Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1

被引：75

作者：

Kameshita, Isamu ^{[1
]}

Sekiguchi, Mari ^{[1
]}

Hamasaki, Daisuke ^{[1
]}

Sugiyama, Yasunori ^{[1
]}

Hatano, Naoya ^{[2
]}

Suetake, Isao ^{[3
]}

Tajima, Shoji ^{[3
]}

Sueyoshi, Noriyuki ^{[1
]}

机构：

[1] Kagawa Univ, Dept Life Sci, Fac Agr, Miki, Kagawa 7610795, Japan

[2] Kagawa Univ, Rare Sugar Res Ctr, Kagawa 7610793, Japan

[3] Osaka Univ, Inst Prot Res, Lab Epigenet, Osaka 5650871, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 377卷 / 04期

关键词：

DNA methylation; DNA methyltransferase; Protein phosphorylation; Cyclin-dependent kinase-like 5; Protein kinase; MeCP2; DNA-binding protein;

D O I：

10.1016/j.bbrc.2008.10.113

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：

DNA methyltransferase 1 (Dnmt1) is an enzyme that recognizes and methylates hemimethylated CpG after DNA replication to maintain methylation patterns. Although the N-terminal region of Dnmt1 is known to interact with various proteins, such as methyl-CpG-binding protein 2 (MeCP2). the associations of protein kinases with this region have not been reported. In the present study, we found that a 110-kDa protein kinase in mouse brain could bind to the N-terminal domain of Dnmt1. This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found to colocalize in nuclei and appeared to interact with each other. Catalytically active CDKL5, CDKL5(1-352), phosphorylated the N-terminal region of Dnmt1 in the presence of DNA. Considering that defects in the MeCP2 or CDKL5 genes cause Rett syndrome, we propose that the interaction between Dnmt1 and CDKL5 may contribute to the pathogenic processes of Rett syndrome. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：1162 / 1167

页数：6

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