细胞周期蛋白依赖激酶1
Cdc25型
细胞周期
细胞生长
细胞生物学
化学
激酶
锌
生物
生物化学
细胞
有机化学
作者
Lu Sun,Yingtao Chai,Robyn Hannigan,Venkata K. Bhogaraju,Khaled Machaca
摘要
Abstract Zn 2+ is an essential micronutrient for the growth and development of multicellular organisms, as Zn 2+ deficiencies lead to growth retardation and congenital malformations (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79–118). At the cellular level Zn 2+ depravation results in proliferation defects in many cell types (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79–118), however the molecular pathways involved remain poorly defined. Here we show that the transition metal chelator TPEN ( N , N , N ′, N ′‐tetrakis(2‐pyridylmethyl) ethylene diamine) blocks the G2/M transition of the meiotic cell cycle by inhibiting Cdc25C‐cdk1 activation. ICP‐MS analyses reveal that Cdc25C is a Zn 2+ ‐binding metalloprotein, and that TPEN effectively strips Zn 2+ away from the enzyme. Interestingly, although apo‐Cdc25C (Zn 2+ ‐deficient) remains fully catalytically active, it is compromised in its ability to dephosphorylate and activate MPF/cdk1. Thus, Zn 2+ is an important regulator of Cdc25C function in vivo. Because of the conserved essential role of the Cdc25C‐cdk1 module in the eukaryotic cell cycle, these studies provide fundamental insights into cell cycle regulation. J. Cell. Physiol. 213: 98–104, 2007. © 2007 Wiley‐Liss, Inc.
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