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Hsp90ß interacts with MDM2 to suppress p53-dependent senescence during skeletal muscle regeneration.
He, Min Yi; Xu, Shui Bo; Qu, Zi Hao; Guo, Yue Mei; Liu, Xiao Ceng; Cong, Xiao Xia; Wang, Jian Feng; Low, Boon Chuan; Li, Li; Wu, Qiang; Lin, Peng; Yan, Shi Gui; Bao, Zhang; Zhou, Yi Ting; Zheng, Li Ling.
Afiliación
  • He MY; Department of Biochemistry and Molecular Biology, Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xu SB; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • Qu ZH; Department of Biochemistry and Molecular Biology, Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Guo YM; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • Liu XC; Department of Biochemistry and Molecular Biology, Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Cong XX; Department of Biochemistry and Molecular Biology, Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Wang JF; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • Low BC; Department of Biochemistry and Molecular Biology, Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Li L; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • Wu Q; Department of Biochemistry and Molecular Biology, Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Lin P; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • Yan SG; Department of Respiratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Bao Z; Mechanobiology Institute, Department of Biological Sciences, National University of Singapore, Singapore.
  • Zhou YT; Institute of Aging Research, Hangzhou Normal University, Hangzhou, China.
  • Zheng LL; The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
Aging Cell ; 18(5): e13003, 2019 10.
Article en En | MEDLINE | ID: mdl-31313490
Cellular senescence plays both beneficial and detrimental roles in embryonic development and tissue regeneration, while the underlying mechanism remains elusive. Recent studies disclosed the emerging roles of heat-shock proteins in regulating muscle regeneration and homeostasis. Here, we found that Hsp90ß, but not Hsp90α isoform, was significantly upregulated during muscle regeneration. RNA-seq analysis disclosed a transcriptional elevation of p21 in Hsp90ß-depleted myoblasts, which is due to the upregulation of p53. Moreover, knockdown of Hsp90ß in myoblasts resulted in p53-dependent cellular senescence. In contrast to the notion that Hsp90 interacts with and protects mutant p53 in cancer, Hsp90ß preferentially bound to wild-type p53 and modulated its degradation via a proteasome-dependent manner. Moreover, Hsp90ß interacted with MDM2, the chief E3 ligase of p53, to regulate the stability of p53. In line with these in vitro studies, the expression level of p53-p21 axis was negatively correlated with Hsp90ß in aged mice muscle. Consistently, administration of 17-AAG, a Hsp90 inhibitor under clinical trial, impaired muscle regeneration by enhancing injury-induced senescence in vivo. Taken together, our finding revealed a previously unappreciated role of Hsp90ß in regulating p53 stability to suppress senescence both in vitro and in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Senescencia Celular / Músculo Esquelético / Proteínas HSP90 de Choque Térmico / Proteínas Proto-Oncogénicas c-mdm2 Límite: Animals Idioma: En Revista: Aging Cell Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Senescencia Celular / Músculo Esquelético / Proteínas HSP90 de Choque Térmico / Proteínas Proto-Oncogénicas c-mdm2 Límite: Animals Idioma: En Revista: Aging Cell Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido