Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response
Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this orga...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Martínez-Puente, David H. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019 |
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| Schlagwörter: |
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| Anmerkung: |
© Cell Stress Society International 2019 |
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| Übergeordnetes Werk: |
Enthalten in: Cell stress & chaperones - Dordrecht : Springer, 1996, 24(2019), 1 vom: Jan., Seite 149-158 |
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| Übergeordnetes Werk: |
volume:24 ; year:2019 ; number:1 ; month:01 ; pages:149-158 |
| Links: |
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| DOI / URN: |
10.1007/s12192-018-0952-8 |
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| Katalog-ID: |
SPR025170619 |
|---|
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| 100 | 1 | |a Martínez-Puente, David H. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response |
| 264 | 1 | |c 2019 | |
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| 500 | |a © Cell Stress Society International 2019 | ||
| 520 | |a Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. | ||
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| 650 | 4 | |a KDEL signal |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a ER targeting |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a GRP78/BiP |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Pérez-Trujillo, José J. |4 aut | |
| 700 | 1 | |a Gutiérrez-Puente, Yolanda |4 aut | |
| 700 | 1 | |a Rodríguez-Rocha, Humberto |4 aut | |
| 700 | 1 | |a García-García, Aracely |4 aut | |
| 700 | 1 | |a Saucedo-Cárdenas, Odila |4 aut | |
| 700 | 1 | |a Montes-de-Oca-Luna, Roberto |4 aut | |
| 700 | 1 | |a Loera-Arias, María J. |0 (orcid)0000-0001-9561-3624 |4 aut | |
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| 773 | 1 | 8 | |g volume:24 |g year:2019 |g number:1 |g month:01 |g pages:149-158 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1007/s12192-018-0952-8 |z lizenzpflichtig |3 Volltext |
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10.1007/s12192-018-0952-8 doi (DE-627)SPR025170619 (SPR)s12192-018-0952-8-e DE-627 ger DE-627 rakwb eng Martínez-Puente, David H. verfasserin aut Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cell Stress Society International 2019 Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. E7 (dpeaa)DE-He213 Stress response (dpeaa)DE-He213 Signal peptide (dpeaa)DE-He213 KDEL signal (dpeaa)DE-He213 ER targeting (dpeaa)DE-He213 GRP78/BiP (dpeaa)DE-He213 Pérez-Trujillo, José J. aut Gutiérrez-Puente, Yolanda aut Rodríguez-Rocha, Humberto aut García-García, Aracely aut Saucedo-Cárdenas, Odila aut Montes-de-Oca-Luna, Roberto aut Loera-Arias, María J. (orcid)0000-0001-9561-3624 aut Enthalten in Cell stress & chaperones Dordrecht : Springer, 1996 24(2019), 1 vom: Jan., Seite 149-158 (DE-627)320421309 (DE-600)2002594-4 1466-1268 nnns volume:24 year:2019 number:1 month:01 pages:149-158 https://dx.doi.org/10.1007/s12192-018-0952-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_2939 GBV_ILN_2946 GBV_ILN_2949 GBV_ILN_2951 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4346 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2019 1 01 149-158 |
| spelling |
10.1007/s12192-018-0952-8 doi (DE-627)SPR025170619 (SPR)s12192-018-0952-8-e DE-627 ger DE-627 rakwb eng Martínez-Puente, David H. verfasserin aut Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cell Stress Society International 2019 Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. E7 (dpeaa)DE-He213 Stress response (dpeaa)DE-He213 Signal peptide (dpeaa)DE-He213 KDEL signal (dpeaa)DE-He213 ER targeting (dpeaa)DE-He213 GRP78/BiP (dpeaa)DE-He213 Pérez-Trujillo, José J. aut Gutiérrez-Puente, Yolanda aut Rodríguez-Rocha, Humberto aut García-García, Aracely aut Saucedo-Cárdenas, Odila aut Montes-de-Oca-Luna, Roberto aut Loera-Arias, María J. (orcid)0000-0001-9561-3624 aut Enthalten in Cell stress & chaperones Dordrecht : Springer, 1996 24(2019), 1 vom: Jan., Seite 149-158 (DE-627)320421309 (DE-600)2002594-4 1466-1268 nnns volume:24 year:2019 number:1 month:01 pages:149-158 https://dx.doi.org/10.1007/s12192-018-0952-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_2939 GBV_ILN_2946 GBV_ILN_2949 GBV_ILN_2951 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4346 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2019 1 01 149-158 |
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10.1007/s12192-018-0952-8 doi (DE-627)SPR025170619 (SPR)s12192-018-0952-8-e DE-627 ger DE-627 rakwb eng Martínez-Puente, David H. verfasserin aut Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cell Stress Society International 2019 Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. E7 (dpeaa)DE-He213 Stress response (dpeaa)DE-He213 Signal peptide (dpeaa)DE-He213 KDEL signal (dpeaa)DE-He213 ER targeting (dpeaa)DE-He213 GRP78/BiP (dpeaa)DE-He213 Pérez-Trujillo, José J. aut Gutiérrez-Puente, Yolanda aut Rodríguez-Rocha, Humberto aut García-García, Aracely aut Saucedo-Cárdenas, Odila aut Montes-de-Oca-Luna, Roberto aut Loera-Arias, María J. (orcid)0000-0001-9561-3624 aut Enthalten in Cell stress & chaperones Dordrecht : Springer, 1996 24(2019), 1 vom: Jan., Seite 149-158 (DE-627)320421309 (DE-600)2002594-4 1466-1268 nnns volume:24 year:2019 number:1 month:01 pages:149-158 https://dx.doi.org/10.1007/s12192-018-0952-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_2939 GBV_ILN_2946 GBV_ILN_2949 GBV_ILN_2951 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4346 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2019 1 01 149-158 |
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10.1007/s12192-018-0952-8 doi (DE-627)SPR025170619 (SPR)s12192-018-0952-8-e DE-627 ger DE-627 rakwb eng Martínez-Puente, David H. verfasserin aut Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cell Stress Society International 2019 Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. E7 (dpeaa)DE-He213 Stress response (dpeaa)DE-He213 Signal peptide (dpeaa)DE-He213 KDEL signal (dpeaa)DE-He213 ER targeting (dpeaa)DE-He213 GRP78/BiP (dpeaa)DE-He213 Pérez-Trujillo, José J. aut Gutiérrez-Puente, Yolanda aut Rodríguez-Rocha, Humberto aut García-García, Aracely aut Saucedo-Cárdenas, Odila aut Montes-de-Oca-Luna, Roberto aut Loera-Arias, María J. (orcid)0000-0001-9561-3624 aut Enthalten in Cell stress & chaperones Dordrecht : Springer, 1996 24(2019), 1 vom: Jan., Seite 149-158 (DE-627)320421309 (DE-600)2002594-4 1466-1268 nnns volume:24 year:2019 number:1 month:01 pages:149-158 https://dx.doi.org/10.1007/s12192-018-0952-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_2939 GBV_ILN_2946 GBV_ILN_2949 GBV_ILN_2951 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4346 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2019 1 01 149-158 |
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10.1007/s12192-018-0952-8 doi (DE-627)SPR025170619 (SPR)s12192-018-0952-8-e DE-627 ger DE-627 rakwb eng Martínez-Puente, David H. verfasserin aut Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Cell Stress Society International 2019 Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. E7 (dpeaa)DE-He213 Stress response (dpeaa)DE-He213 Signal peptide (dpeaa)DE-He213 KDEL signal (dpeaa)DE-He213 ER targeting (dpeaa)DE-He213 GRP78/BiP (dpeaa)DE-He213 Pérez-Trujillo, José J. aut Gutiérrez-Puente, Yolanda aut Rodríguez-Rocha, Humberto aut García-García, Aracely aut Saucedo-Cárdenas, Odila aut Montes-de-Oca-Luna, Roberto aut Loera-Arias, María J. (orcid)0000-0001-9561-3624 aut Enthalten in Cell stress & chaperones Dordrecht : Springer, 1996 24(2019), 1 vom: Jan., Seite 149-158 (DE-627)320421309 (DE-600)2002594-4 1466-1268 nnns volume:24 year:2019 number:1 month:01 pages:149-158 https://dx.doi.org/10.1007/s12192-018-0952-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_2939 GBV_ILN_2946 GBV_ILN_2949 GBV_ILN_2951 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4346 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2019 1 01 149-158 |
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English |
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Enthalten in Cell stress & chaperones 24(2019), 1 vom: Jan., Seite 149-158 volume:24 year:2019 number:1 month:01 pages:149-158 |
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Enthalten in Cell stress & chaperones 24(2019), 1 vom: Jan., Seite 149-158 volume:24 year:2019 number:1 month:01 pages:149-158 |
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E7 Stress response Signal peptide KDEL signal ER targeting GRP78/BiP |
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Cell stress & chaperones |
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Martínez-Puente, David H. @@aut@@ Pérez-Trujillo, José J. @@aut@@ Gutiérrez-Puente, Yolanda @@aut@@ Rodríguez-Rocha, Humberto @@aut@@ García-García, Aracely @@aut@@ Saucedo-Cárdenas, Odila @@aut@@ Montes-de-Oca-Luna, Roberto @@aut@@ Loera-Arias, María J. @@aut@@ |
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2019-01-01T00:00:00Z |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR025170619</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519090411.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s12192-018-0952-8</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR025170619</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12192-018-0952-8-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Martínez-Puente, David H.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Cell Stress Society International 2019</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. 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| author |
Martínez-Puente, David H. |
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Martínez-Puente, David H. misc E7 misc Stress response misc Signal peptide misc KDEL signal misc ER targeting misc GRP78/BiP Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response |
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1466-1268 |
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Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response E7 (dpeaa)DE-He213 Stress response (dpeaa)DE-He213 Signal peptide (dpeaa)DE-He213 KDEL signal (dpeaa)DE-He213 ER targeting (dpeaa)DE-He213 GRP78/BiP (dpeaa)DE-He213 |
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misc E7 misc Stress response misc Signal peptide misc KDEL signal misc ER targeting misc GRP78/BiP |
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misc E7 misc Stress response misc Signal peptide misc KDEL signal misc ER targeting misc GRP78/BiP |
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Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response |
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Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response |
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Martínez-Puente, David H. |
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Cell stress & chaperones |
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Martínez-Puente, David H. Pérez-Trujillo, José J. Gutiérrez-Puente, Yolanda Rodríguez-Rocha, Humberto García-García, Aracely Saucedo-Cárdenas, Odila Montes-de-Oca-Luna, Roberto Loera-Arias, María J. |
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Elektronische Aufsätze |
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Martínez-Puente, David H. |
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10.1007/s12192-018-0952-8 |
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(ORCID)0000-0001-9561-3624 |
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targeting hpv-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response |
| title_auth |
Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response |
| abstract |
Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. © Cell Stress Society International 2019 |
| abstractGer |
Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. © Cell Stress Society International 2019 |
| abstract_unstemmed |
Abstract Very promising results have been observed with a deoxyribonucleic acid (DNA) vaccine based on human papillomavirus type-16 (HPV-16) antigen retention and delivery system in the endoplasmic reticulum (ER). However, the mechanism by which these antigens are processed once they reach this organelle is still unknown. Therefore, we evaluated whether this system awakens a stress response in the ER. Different DNA constructs based on E6 and E7 mutant antigens fused to an ER signal peptide (SP), a signal for retention in the ER (KDEL), or both signals (SPK), were transfected into HEK-293 cells. Overexpression of E6 and E7 antigens targeted to the ER (SP, and SPK constructs) induced ER stress, which was indicated by an increase of the ER-stress markers GRP78/BiP and CHOP. Additionally, the ER stress response was mediated by the ATF4 transcription factor, which was translocated into the nucleus. Besides, the overexpressed antigens were degraded by the proteasome. Through a cycloheximide-chase assay, we demonstrated that when both protein synthesis and proteasome were inhibited, the overexpressed antigens were degraded. Interestingly, when proteasome was blocked autophagy was increased and the ER stress response decreased. Taken together, these results indicate that the antigens are initially degraded by the ERAD pathway, and autophagy degradation pathway can be induced to compensate the proteasome inhibition. Therefore, we provided a new insight into the mechanism by which E6 and E7 mutant antigens are processed once they reach the ER, which will help to improve the development of more effective vaccines against cancer. © Cell Stress Society International 2019 |
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Targeting HPV-16 antigens to the endoplasmic reticulum induces an endoplasmic reticulum stress response |
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Pérez-Trujillo, José J. Gutiérrez-Puente, Yolanda Rodríguez-Rocha, Humberto García-García, Aracely Saucedo-Cárdenas, Odila Montes-de-Oca-Luna, Roberto Loera-Arias, María J. |
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| score |
7.3995056 |