Journal
EMBO REPORTS
Volume 10, Issue 12, Pages 1327-1333Publisher
WILEY
DOI: 10.1038/embor.2009.217
Keywords
HIPK2; MeCP2; phosphorylation; apoptosis
Categories
Funding
- National Institutes of Health [NS048276, NS058391]
- Italy-USA Program for Rare Diseases
- Associazione Italiana per la Ricerca sul Cancro
- Rett Syndrome Research Foundation
- Telethon
- Fondazione Cariplo
- E-Rare EuroRETT network
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Mutations in the methyl-CpG-binding protein 2 (MeCP2) are associated with Rett syndrome and other neurological disorders. MeCP2 represses transcription mainly by recruiting various corepressor complexes. Recently, MeCP2 phosphorylation at Ser 80, Ser 229 and Ser 421 was shown to occur in the brain and modulate MeCP2 silencing activities. However, the kinases directly responsible for this are largely unknown. Here, we identify the homeodomain-interacting protein kinase 2 (HIPK2) as a kinase that binds MeCP2 and phosphorylates it at Ser 80 in vitro and in vivo. HIPK2 modulates cell proliferation and apoptosis, and the neurological defects of Hipk2-null mice indicate its role in proper brain functions. We show that MeCP2 cooperates with HIPK2 in induction of apoptosis and that Ser 80 phosphorylation is required together with the DNA binding of MeCP2. These data are, to our knowledge, the first that describe a kinase associating with MeCP2, causing its specific phosphorylation in vivo and, furthermore, they reinforce the role of MeCP2 in regulating cell growth.
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