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Methyl-CpG-binding protein 2 is phosphorylated by homeodomain-interacting protein kinase 2 and contributes to apoptosis
被引:46
作者:

Bracaglia, Giorgia
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机构:
Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

Conca, Barbara
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h-index: 0
机构:
Univ Insubria, Dept Struct & Funct Biol, Lab Genet & Epigenet Control Gene Express, I-21052 Busto Arsizio, VA, Italy Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

Bergo, Anna
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机构:
Univ Insubria, Dept Struct & Funct Biol, Lab Genet & Epigenet Control Gene Express, I-21052 Busto Arsizio, VA, Italy Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

Rusconi, Laura
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机构:
Univ Insubria, Dept Struct & Funct Biol, Lab Genet & Epigenet Control Gene Express, I-21052 Busto Arsizio, VA, Italy Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

Zhou, Zhaolan
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机构:
Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

Greenberg, Michael E.
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机构:
Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

Landsberger, Nicoletta
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Insubria, Dept Struct & Funct Biol, Lab Genet & Epigenet Control Gene Express, I-21052 Busto Arsizio, VA, Italy
Hosp San Raffaele, Div Neurosci, San Raffaele Rett Res Ctr, I-20132 Milan, Italy Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

Soddu, Silvia
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h-index: 0
机构:
Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy

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机构:
[1] Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Dept Expt Oncol, I-00158 Rome, Italy
[2] Univ Insubria, Dept Struct & Funct Biol, Lab Genet & Epigenet Control Gene Express, I-21052 Busto Arsizio, VA, Italy
[3] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[4] Hosp San Raffaele, Div Neurosci, San Raffaele Rett Res Ctr, I-20132 Milan, Italy
基金:
美国国家卫生研究院;
关键词:
HIPK2;
MeCP2;
phosphorylation;
apoptosis;
FUNCTIONAL CONSEQUENCES;
BDNF TRANSCRIPTION;
RETT-SYNDROME;
HIPK2;
MECP2;
MUTATIONS;
GROWTH;
CDKL5;
D O I:
10.1038/embor.2009.217
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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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收藏
页码:1327 / 1333
页数:7
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Bergo, A
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Badaracco, G
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Zappella, M
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Broccoli, V
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Renieri, A
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Kilstrup-Nielsen, C
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Landsberger, N
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Univ Insubria, Dipartimento Biol Strutturale & Funz, I-21052 Busto Arsizio, VA, Italy Univ Insubria, Dipartimento Biol Strutturale & Funz, I-21052 Busto Arsizio, VA, Italy