Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / physiology
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Animals
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Apoptosis / physiology
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Cell Line
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DNA-Binding Proteins / metabolism
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Histone Deacetylases / chemistry
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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In Vitro Techniques
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Mice
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Mice, Inbred BALB C
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Myosin-Light-Chain Kinase / genetics
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Myosin-Light-Chain Kinase / metabolism
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Myosin-Light-Chain Phosphatase / antagonists & inhibitors
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Myosin-Light-Chain Phosphatase / genetics
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Myosin-Light-Chain Phosphatase / metabolism*
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism
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Phosphorylation
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Protein Phosphatase 1
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RNA, Small Interfering / genetics
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Steroid / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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T-Lymphocytes / cytology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / enzymology*
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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Nr4a1 protein, mouse
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Nuclear Receptor Subfamily 4, Group A, Member 1
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RNA, Small Interfering
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Receptors, Antigen, T-Cell
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Recombinant Proteins
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Transcription Factors
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Myosin-Light-Chain Kinase
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Phosphoprotein Phosphatases
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Protein Phosphatase 1
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Myosin-Light-Chain Phosphatase
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Ppp1r12a protein, mouse
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Hdac7 protein, mouse
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Histone Deacetylases
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Tetradecanoylphorbol Acetate