期刊
GENES & DEVELOPMENT
卷 21, 期 6, 页码 638-643出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1513107
关键词
HDAC7; myosin phosphatase; nucleocytoplasmic shuttling; thymocytes
资金
- NCRR NIH HHS [RR 18928-01, C06 RR018928] Funding Source: Medline
The repressive activity of histone deacetylase 7 (HDAC7), a class IIa HDAC expressed in CD4(+)CD8(+) double-positive thymocytes, is regulated by its nucleocytoplasmic shuttling. In resting thymocytes, HDAC7 is nuclear and functions as a transcriptional repressor. After T-cell receptor (TCR) activation, the serine/threonine kinase PKD1 phosphorylates HDAC7, resulting in its nuclear export and the derepression of its target genes. Here, we identify protein phosphatase 1 beta (PP1 beta) and myosin phosphatase targeting subunit 1 (MYPT1), two components of the myosin phosphatase complex, as HDAC7-associated proteins in thymocytes. Myosin phosphatase dephosphorylates HDAC7 and promotes its nuclear localization, leading to the repression of the HDAC7 target, Nur77, and the inhibition of apoptosis in CD4(+)CD8(+) thymocytes.
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