BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response

Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa...
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Autor*in:	Ji, Rui [verfasserIn] Zhang, Zhimo Yang, Zhe Chen, Xin Yin, Tailang Yang, Jing

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Polycystic ovary syndrome (PCOS) Block of proliferation 1 (BOP1) Autophagy Nucleolus stress

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Cellular and molecular life sciences - Cham (ZG) : Springer International Publishing AG, 1997, 81(2024), 1 vom: 27. Feb.
Übergeordnetes Werk:	volume:81 ; year:2024 ; number:1 ; day:27 ; month:02

Links:	Volltext

DOI / URN:	10.1007/s00018-023-05091-1

Katalog-ID:	SPR054896479

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520			\|a Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS.
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allfields	10.1007/s00018-023-05091-1 doi (DE-627)SPR054896479 (SPR)s00018-023-05091-1-e DE-627 ger DE-627 rakwb eng Ji, Rui verfasserin aut BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. Polycystic ovary syndrome (PCOS) (dpeaa)DE-He213 Block of proliferation 1 (BOP1) (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Nucleolus stress (dpeaa)DE-He213 Zhang, Zhimo aut Yang, Zhe aut Chen, Xin aut Yin, Tailang aut Yang, Jing (orcid)0000-0002-3286-0772 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 81(2024), 1 vom: 27. Feb. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:27 month:02 https://dx.doi.org/10.1007/s00018-023-05091-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 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 81 2024 1 27 02
spelling	10.1007/s00018-023-05091-1 doi (DE-627)SPR054896479 (SPR)s00018-023-05091-1-e DE-627 ger DE-627 rakwb eng Ji, Rui verfasserin aut BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. Polycystic ovary syndrome (PCOS) (dpeaa)DE-He213 Block of proliferation 1 (BOP1) (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Nucleolus stress (dpeaa)DE-He213 Zhang, Zhimo aut Yang, Zhe aut Chen, Xin aut Yin, Tailang aut Yang, Jing (orcid)0000-0002-3286-0772 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 81(2024), 1 vom: 27. Feb. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:27 month:02 https://dx.doi.org/10.1007/s00018-023-05091-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 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 81 2024 1 27 02
allfields_unstemmed	10.1007/s00018-023-05091-1 doi (DE-627)SPR054896479 (SPR)s00018-023-05091-1-e DE-627 ger DE-627 rakwb eng Ji, Rui verfasserin aut BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. Polycystic ovary syndrome (PCOS) (dpeaa)DE-He213 Block of proliferation 1 (BOP1) (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Nucleolus stress (dpeaa)DE-He213 Zhang, Zhimo aut Yang, Zhe aut Chen, Xin aut Yin, Tailang aut Yang, Jing (orcid)0000-0002-3286-0772 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 81(2024), 1 vom: 27. Feb. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:27 month:02 https://dx.doi.org/10.1007/s00018-023-05091-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 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 81 2024 1 27 02
allfieldsGer	10.1007/s00018-023-05091-1 doi (DE-627)SPR054896479 (SPR)s00018-023-05091-1-e DE-627 ger DE-627 rakwb eng Ji, Rui verfasserin aut BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. Polycystic ovary syndrome (PCOS) (dpeaa)DE-He213 Block of proliferation 1 (BOP1) (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Nucleolus stress (dpeaa)DE-He213 Zhang, Zhimo aut Yang, Zhe aut Chen, Xin aut Yin, Tailang aut Yang, Jing (orcid)0000-0002-3286-0772 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 81(2024), 1 vom: 27. Feb. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:27 month:02 https://dx.doi.org/10.1007/s00018-023-05091-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 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 81 2024 1 27 02
allfieldsSound	10.1007/s00018-023-05091-1 doi (DE-627)SPR054896479 (SPR)s00018-023-05091-1-e DE-627 ger DE-627 rakwb eng Ji, Rui verfasserin aut BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. Polycystic ovary syndrome (PCOS) (dpeaa)DE-He213 Block of proliferation 1 (BOP1) (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Nucleolus stress (dpeaa)DE-He213 Zhang, Zhimo aut Yang, Zhe aut Chen, Xin aut Yin, Tailang aut Yang, Jing (orcid)0000-0002-3286-0772 aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 81(2024), 1 vom: 27. Feb. (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:81 year:2024 number:1 day:27 month:02 https://dx.doi.org/10.1007/s00018-023-05091-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_267 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2005 GBV_ILN_2014 GBV_ILN_2021 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4246 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 81 2024 1 27 02
language	English
source	Enthalten in Cellular and molecular life sciences 81(2024), 1 vom: 27. Feb. volume:81 year:2024 number:1 day:27 month:02
sourceStr	Enthalten in Cellular and molecular life sciences 81(2024), 1 vom: 27. Feb. volume:81 year:2024 number:1 day:27 month:02
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Polycystic ovary syndrome (PCOS) Block of proliferation 1 (BOP1) Autophagy Nucleolus stress
isfreeaccess_bool	true
container_title	Cellular and molecular life sciences
authorswithroles_txt_mv	Ji, Rui @@aut@@ Zhang, Zhimo @@aut@@ Yang, Zhe @@aut@@ Chen, Xin @@aut@@ Yin, Tailang @@aut@@ Yang, Jing @@aut@@
publishDateDaySort_date	2024-02-27T00:00:00Z
hierarchy_top_id	253390524
id	SPR054896479
language_de	englisch
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author	Ji, Rui
spellingShingle	Ji, Rui misc Polycystic ovary syndrome (PCOS) misc Block of proliferation 1 (BOP1) misc Autophagy misc Nucleolus stress BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response
authorStr	Ji, Rui
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topic_title	BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response Polycystic ovary syndrome (PCOS) (dpeaa)DE-He213 Block of proliferation 1 (BOP1) (dpeaa)DE-He213 Autophagy (dpeaa)DE-He213 Nucleolus stress (dpeaa)DE-He213
topic	misc Polycystic ovary syndrome (PCOS) misc Block of proliferation 1 (BOP1) misc Autophagy misc Nucleolus stress
topic_unstemmed	misc Polycystic ovary syndrome (PCOS) misc Block of proliferation 1 (BOP1) misc Autophagy misc Nucleolus stress
topic_browse	misc Polycystic ovary syndrome (PCOS) misc Block of proliferation 1 (BOP1) misc Autophagy misc Nucleolus stress
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title	BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response
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title_full	BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response
author_sort	Ji, Rui
journal	Cellular and molecular life sciences
journalStr	Cellular and molecular life sciences
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author_browse	Ji, Rui Zhang, Zhimo Yang, Zhe Chen, Xin Yin, Tailang Yang, Jing
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author-letter	Ji, Rui
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title_sort	bop1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response
title_auth	BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response
abstract	Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. © The Author(s) 2024
abstractGer	Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. © The Author(s) 2024
abstract_unstemmed	Abstract Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS. © The Author(s) 2024
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title_short	BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response
url	https://dx.doi.org/10.1007/s00018-023-05091-1
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author2	Zhang, Zhimo Yang, Zhe Chen, Xin Yin, Tailang Yang, Jing
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