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 co-repressor 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.

Methyl-CpG-binding protein 2 is phosphorylated by homeodomain-interacting protein kinase 2 and contributes to apoptosis / G. Bracaglia, B. Conca, A. Bergo, L. Rusconi, Z. Zhou, M.E. Greenberg, N. Landsberger, S. Soddu, C. Kilstrup-Nielsen. - In: EMBO REPORTS. - ISSN 1469-221X. - 10:12(2009), pp. 1327-1333. [10.1038/embor.2009.217]

Methyl-CpG-binding protein 2 is phosphorylated by homeodomain-interacting protein kinase 2 and contributes to apoptosis

N. Landsberger;
2009

Abstract

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 co-repressor 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.
English
Apoptosis; HIPK2; MeCP2; Phosphorylation; Amino Acid Substitution; Animals; Apoptosis; Carrier Proteins; Cells, Cultured; DNA; Embryo, Mammalian; HeLa Cells; Humans; Methyl-CpG-Binding Protein 2; Mice; Mutant Proteins; NIH 3T3 Cells; Phosphorylation; Protein Binding; Protein-Serine-Threonine Kinases; RNA, Small Interfering; Serine
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Pubblicazione scientifica
2009
WILEY
10
12
1327
1333
7
Pubblicato
Periodico con rilevanza internazionale
scopus
pubmed
crossref
wos
datacite
Aderisco
info:eu-repo/semantics/article
Methyl-CpG-binding protein 2 is phosphorylated by homeodomain-interacting protein kinase 2 and contributes to apoptosis / G. Bracaglia, B. Conca, A. Bergo, L. Rusconi, Z. Zhou, M.E. Greenberg, N. Landsberger, S. Soddu, C. Kilstrup-Nielsen. - In: EMBO REPORTS. - ISSN 1469-221X. - 10:12(2009), pp. 1327-1333. [10.1038/embor.2009.217]
open
Prodotti della ricerca::01 - Articolo su periodico
9
262
Article (author)
no
G. Bracaglia, B. Conca, A. Bergo, L. Rusconi, Z. Zhou, M.E. Greenberg, N. Landsberger, S. Soddu, C. Kilstrup-Nielsen
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/816771
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