Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes.
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 1beta (PP1beta) 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.
Parra
Maribel
M
Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, California 94158, USA.
Mahmoudi
Tokameh
T
Verdin
Eric
E
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D034741:RNA, Small Interfering / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D014157:Transcription Factors; D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D043263:Myosin-Light-Chain Phosphatase; C510645:Ppp1r12a protein, mouse; C543274:Hdac7 protein, mouse; D006655:Histone Deacetylases; D013755:Tetradecanoylphorbol Acetate