Caratterizzazione fisica e funzionale della nuova interazione tra la chinasi pro-apoptotica HIPK2 e il fattore associato alla Sindrome di Rett, MeCP2
Author(s)
Bracaglia, Giorgia
Date Issued
February 8, 2011
Type
Doctoral Thesis
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 corepressor complexes. Recently, MeCP2 phosphorylation at Ser 80, Ser 229 AND Ser 421 was shown to occur in the brain and modulate MeCP2 silencing activies. However. The kinases directly responsible for this are largely unknow. Here we identify the homeodomain-interactin protein kinase-2 (HIPK2) as a kinase that binds MeCP2 and phosphorylates it at Ser80 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.
Additional information
Dottorato di ricerca in Genetica e biologia cellulare
Subjects
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