Cargando…

HDAC8 cooperates with SMAD3/4 complex to suppress SIRT7 and promote cell survival and migration

NAD(+)-dependent SIRT7 deacylase plays essential roles in ribosome biogenesis, stress response, genome integrity, metabolism and aging, while how it is transcriptionally regulated is still largely unclear. TGF-β signaling is highly conserved in multicellular organisms, regulating cell growth, cancer...

Descripción completa

Detalles Bibliográficos
Autores principales: Tang, Xiaolong, Li, Guo, Su, Fengting, Cai, Yanlin, Shi, Lei, Meng, Yuan, Liu, Zuojun, Sun, Jie, Wang, Ming, Qian, Minxian, Wang, Zimei, Xu, Xingzhi, Cheng, Yong-Xian, Zhu, Wei-Guo, Liu, Baohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102950/
https://www.ncbi.nlm.nih.gov/pubmed/31970414
http://dx.doi.org/10.1093/nar/gkaa039
Descripción
Sumario:NAD(+)-dependent SIRT7 deacylase plays essential roles in ribosome biogenesis, stress response, genome integrity, metabolism and aging, while how it is transcriptionally regulated is still largely unclear. TGF-β signaling is highly conserved in multicellular organisms, regulating cell growth, cancer stemness, migration and invasion. Here, we demonstrate that histone deacetylase HDAC8 forms complex with SMAD3/4 heterotrimer and occupies SIRT7 promoter, wherein it deacetylates H4 and thus suppresses SIRT7 transcription. Treatment with HDAC8 inhibitor compromises TGF-β signaling via SIRT7-SMAD4 axis and consequently, inhibits lung metastasis and improves chemotherapy efficacy in breast cancer. Our data establish a regulatory feedback loop of TGF-β signaling, wherein HDAC8 as a novel cofactor of SMAD3/4 complex, transcriptionally suppresses SIRT7 via local chromatin remodeling and thus further activates TGF-β signaling. Targeting HDAC8 exhibits therapeutic potential for TGF-β signaling related diseases.