Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α

Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spr...
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Autor*in:	Maida, Immacolata [verfasserIn] Zanna, Paola Guida, Stefania Ferretta, Anna Cocco, Tiziana Palese, Luigi Leonardo Londei, Paola Benelli, Dario Azzariti, Amalia Tommasi, Stefania Guida, Michele Pellacani, Giovanni Guida, Gabriella

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Metastatic melanoma eIF2α BRAF MiT family Nuclear peIF2α Structural analysis

Anmerkung:	© The Author(s) 2019

Übergeordnetes Werk:	Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 17(2019), 1 vom: 11. Jan.
Übergeordnetes Werk:	volume:17 ; year:2019 ; number:1 ; day:11 ; month:01

Links:	Volltext

DOI / URN:	10.1186/s12967-019-1772-z

Katalog-ID:	SPR02897042X

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520			\|a Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma.
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allfields	10.1186/s12967-019-1772-z doi (DE-627)SPR02897042X (SPR)s12967-019-1772-z-e DE-627 ger DE-627 rakwb eng Maida, Immacolata verfasserin aut Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. Metastatic melanoma (dpeaa)DE-He213 eIF2α (dpeaa)DE-He213 BRAF (dpeaa)DE-He213 MiT family (dpeaa)DE-He213 Nuclear peIF2α (dpeaa)DE-He213 Structural analysis (dpeaa)DE-He213 Zanna, Paola aut Guida, Stefania aut Ferretta, Anna aut Cocco, Tiziana aut Palese, Luigi Leonardo aut Londei, Paola aut Benelli, Dario aut Azzariti, Amalia aut Tommasi, Stefania aut Guida, Michele aut Pellacani, Giovanni aut Guida, Gabriella aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 17(2019), 1 vom: 11. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:17 year:2019 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12967-019-1772-z kostenfrei 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11 01
spelling	10.1186/s12967-019-1772-z doi (DE-627)SPR02897042X (SPR)s12967-019-1772-z-e DE-627 ger DE-627 rakwb eng Maida, Immacolata verfasserin aut Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. Metastatic melanoma (dpeaa)DE-He213 eIF2α (dpeaa)DE-He213 BRAF (dpeaa)DE-He213 MiT family (dpeaa)DE-He213 Nuclear peIF2α (dpeaa)DE-He213 Structural analysis (dpeaa)DE-He213 Zanna, Paola aut Guida, Stefania aut Ferretta, Anna aut Cocco, Tiziana aut Palese, Luigi Leonardo aut Londei, Paola aut Benelli, Dario aut Azzariti, Amalia aut Tommasi, Stefania aut Guida, Michele aut Pellacani, Giovanni aut Guida, Gabriella aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 17(2019), 1 vom: 11. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:17 year:2019 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12967-019-1772-z kostenfrei 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11 01
allfields_unstemmed	10.1186/s12967-019-1772-z doi (DE-627)SPR02897042X (SPR)s12967-019-1772-z-e DE-627 ger DE-627 rakwb eng Maida, Immacolata verfasserin aut Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. Metastatic melanoma (dpeaa)DE-He213 eIF2α (dpeaa)DE-He213 BRAF (dpeaa)DE-He213 MiT family (dpeaa)DE-He213 Nuclear peIF2α (dpeaa)DE-He213 Structural analysis (dpeaa)DE-He213 Zanna, Paola aut Guida, Stefania aut Ferretta, Anna aut Cocco, Tiziana aut Palese, Luigi Leonardo aut Londei, Paola aut Benelli, Dario aut Azzariti, Amalia aut Tommasi, Stefania aut Guida, Michele aut Pellacani, Giovanni aut Guida, Gabriella aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 17(2019), 1 vom: 11. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:17 year:2019 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12967-019-1772-z kostenfrei 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11 01
allfieldsGer	10.1186/s12967-019-1772-z doi (DE-627)SPR02897042X (SPR)s12967-019-1772-z-e DE-627 ger DE-627 rakwb eng Maida, Immacolata verfasserin aut Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. Metastatic melanoma (dpeaa)DE-He213 eIF2α (dpeaa)DE-He213 BRAF (dpeaa)DE-He213 MiT family (dpeaa)DE-He213 Nuclear peIF2α (dpeaa)DE-He213 Structural analysis (dpeaa)DE-He213 Zanna, Paola aut Guida, Stefania aut Ferretta, Anna aut Cocco, Tiziana aut Palese, Luigi Leonardo aut Londei, Paola aut Benelli, Dario aut Azzariti, Amalia aut Tommasi, Stefania aut Guida, Michele aut Pellacani, Giovanni aut Guida, Gabriella aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 17(2019), 1 vom: 11. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:17 year:2019 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12967-019-1772-z kostenfrei 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11 01
allfieldsSound	10.1186/s12967-019-1772-z doi (DE-627)SPR02897042X (SPR)s12967-019-1772-z-e DE-627 ger DE-627 rakwb eng Maida, Immacolata verfasserin aut Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. Metastatic melanoma (dpeaa)DE-He213 eIF2α (dpeaa)DE-He213 BRAF (dpeaa)DE-He213 MiT family (dpeaa)DE-He213 Nuclear peIF2α (dpeaa)DE-He213 Structural analysis (dpeaa)DE-He213 Zanna, Paola aut Guida, Stefania aut Ferretta, Anna aut Cocco, Tiziana aut Palese, Luigi Leonardo aut Londei, Paola aut Benelli, Dario aut Azzariti, Amalia aut Tommasi, Stefania aut Guida, Michele aut Pellacani, Giovanni aut Guida, Gabriella aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 17(2019), 1 vom: 11. Jan. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:17 year:2019 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12967-019-1772-z kostenfrei 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11 01
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author	Maida, Immacolata
spellingShingle	Maida, Immacolata misc Metastatic melanoma misc eIF2α misc BRAF misc MiT family misc Nuclear peIF2α misc Structural analysis Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α
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topic_title	Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α Metastatic melanoma (dpeaa)DE-He213 eIF2α (dpeaa)DE-He213 BRAF (dpeaa)DE-He213 MiT family (dpeaa)DE-He213 Nuclear peIF2α (dpeaa)DE-He213 Structural analysis (dpeaa)DE-He213
topic	misc Metastatic melanoma misc eIF2α misc BRAF misc MiT family misc Nuclear peIF2α misc Structural analysis
topic_unstemmed	misc Metastatic melanoma misc eIF2α misc BRAF misc MiT family misc Nuclear peIF2α misc Structural analysis
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title	Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α
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title_full	Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α
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author_browse	Maida, Immacolata Zanna, Paola Guida, Stefania Ferretta, Anna Cocco, Tiziana Palese, Luigi Leonardo Londei, Paola Benelli, Dario Azzariti, Amalia Tommasi, Stefania Guida, Michele Pellacani, Giovanni Guida, Gabriella
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title_sort	translational control mechanisms in cutaneous malignant melanoma: the role of eif2α
title_auth	Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α
abstract	Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. © The Author(s) 2019
abstractGer	Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. © The Author(s) 2019
abstract_unstemmed	Background Melanoma cells develop adaptive responses in order to cope with particular conditions of tumor microenvironment, characterized by stress conditions and deregulated proliferation. Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. In conclusion, this is the first evidence of nuclear localization of peIF2α, representing a possible target for future therapeutic approaches for metastatic melanoma. © The Author(s) 2019
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title_short	Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α
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author2	Zanna, Paola Guida, Stefania Ferretta, Anna Cocco, Tiziana Palese, Luigi Leonardo Londei, Paola Benelli, Dario Azzariti, Amalia Tommasi, Stefania Guida, Michele Pellacani, Giovanni Guida, Gabriella
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up_date	2024-07-03T22:49:28.460Z
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Recently, the interplay between the stress response and the gene expression programs leading to metastatic spread has been reported. Methods We evaluated levels and localization of eIF2α/peIF2α in V600BRAF and wtBRAF metastatic melanoma cell lines by means of western blot and confocal microscopy analyses. Furthermore, we performed a sequence analyses and structure and dynamics studies of eIF2α protein to reveal the role of eIF2α and its correlations in different pathways involved in the invasive phase of melanoma. Results We found peIF2α both in cytoplasm and nucleus. Nuclear localization was more represented in V600BRAF melanoma cell lines. Our studies on eIF2α protein sequence indicated the presence of a predicted bipartite NLS as well as a nuclear export signal NES and an S1 domain, typical of RNA interacting proteins. Furthermore, we found high levels of transcription factor EB (TFEB), a component of the MiT/TFE family, and low β-catenin levels in V600BRAF cells. Conclusions Based on our results, we suggest that peIF2α nuclear localization can be crucial in ER stress response and in driving the metastatic spread of melanoma, through lysosomal signaling and Wnt/β-catenin pathway. 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Translational control mechanisms in cutaneous malignant melanoma: the role of eIF2α

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