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., 73:79β118). At the cellular level Zn^2+^ depravation results in proliferation defects in many cell types (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79β118), however the molecular pathways involved remain poorly defined. Here we show that the transition metal chelator TPEN (N,N,Nβ²,Nβ²βtetrakis(2βpyridylmethyl) ethylene diamine) blocks the G2/M transition of the meiotic cell cycle by inhibiting Cdc25Cβcdk1 activation. ICPβMS analyses reveal that Cdc25C is a Zn^2+^βbinding metalloprotein, and that TPEN effectively strips Zn^2+^ away from the enzyme. Interestingly, although apoβCdc25C (Zn^2+^βdeficient) 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 Cdc25Cβcdk1 module in the eukaryotic cell cycle, these studies provide fundamental insights into cell cycle regulation. J. Cell. Physiol. 213: 98β104, 2007. Β© 2007 WileyβLiss, Inc.