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PMID:17369396

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Citation

Parra, M, Mahmoudi, T and Verdin, E (2007) Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes. Genes Dev. 21:638-43

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.

Links

PubMed PMC1820937 Online version:10.1101/gad.1513107

Keywords

Active Transport, Cell Nucleus/physiology; Animals; Apoptosis/physiology; Cell Line; DNA-Binding Proteins/metabolism; Histone Deacetylases/chemistry; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Mice; Mice, Inbred BALB C; Myosin-Light-Chain Kinase/genetics; Myosin-Light-Chain Kinase/metabolism; Myosin-Light-Chain Phosphatase/antagonists & inhibitors; Myosin-Light-Chain Phosphatase/genetics; Myosin-Light-Chain Phosphatase/metabolism; Nuclear Receptor Subfamily 4, Group A, Member 1; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/metabolism; Phosphorylation; Protein Phosphatase 1; RNA, Small Interfering/genetics; Receptors, Antigen, T-Cell/metabolism; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Steroid/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; T-Lymphocytes/cytology; T-Lymphocytes/drug effects; T-Lymphocytes/enzymology; Tetradecanoylphorbol Acetate/pharmacology; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PP1G

enables

GO:0004722: protein serine/threonine phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PP1G

involved_in

GO:0006470: protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PP1G

involved_in

GO:0046822: regulation of nucleocytoplasmic transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PP1G

involved_in

GO:0006470: protein dephosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MYPT1

involved_in

GO:0046822: regulation of nucleocytoplasmic transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MYPT1

involved_in

GO:0006470: protein dephosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MYPT1

acts_upstream_of_or_within

GO:0046822: regulation of nucleocytoplasmic transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MYPT1

acts_upstream_of_or_within

GO:0006470: protein dephosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

has_participant:(MGI:MGI:1891835)

Seeded From UniProt

complete


See also

References

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