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PMID:22750291

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Citation

Zhao, Y, Liang, L, Fan, Y, Sun, S, An, L, Shi, Z, Cheng, J, Jia, W, Sun, W, Mori-Akiyama, Y, Zhang, H, Fu, S and Yang, J (2012) PPM1B negatively regulates antiviral response via dephosphorylating TBK1. Cell. Signal. 24:2197-204

Abstract

The production of type I interferon must be tightly regulated and aberrant production of type I interferon is harmful or even fatal to the host. TBK1 phosphorylation at Ser172 plays an essential role in TBK1-mediated antiviral response. However, how TBK1 activity is negatively regulated remains poorly understood. Using a functional genomics approach, we have identified PPM1B as a TBK1 phosphatase. PPM1B dephosphorylates TBK1 in vivo and in vitro. PPM1B wild-type but not its phosphatase-deficient R179G mutant inhibits TBK1-mediated antiviral response and facilitates VSV replication in the cells. Viral infection induces association of PPM1B with TBK1 in a transient fashion in the cells. Conversely, suppression of PPM1B expression enhances virus-induced IRF3 phosphorylation and IFNβ production. Our study identifies a previously unrecognized role for PPM1B in the negative regulation of antiviral response by acting as a TBK1 phosphatase.

Links

PubMed PMC3432707 Online version:10.1016/j.cellsig.2012.06.017

Keywords


Significance

Annotations

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

HUMAN:PPM1B

involved_in

GO:0032688: negative regulation of interferon-beta production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PPM1B

involved_in

GO:0006470: protein dephosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PPM1B

involved_in

GO:0050687: negative regulation of defense response to virus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:C9JIR6

GO:0006470: protein dephosphorylation

ECO:0000315:

P

Fig 3. PPM1B binds to and dephosphorylates TBK1.

complete
CACAO 5866

HUMAN:C9JIR6

involved_in

GO:0006470: protein dephosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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