Zinc regulates the ability of Cdc25C to activate MPF/cdk1

Lu Sun, Yingtao Chai, Robyn Hannigan, Venkata K. Bhogaraju, Khaled Machaca

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Zn2+ is an essential micronutrient for the growth and development of multicellular organisms, as Zn2+ deficiencies lead to growth retardation and congenital malformations (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79-118). At the cellular level Zn2+ depravation results in proliferation defects in many cell types (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79-1 18), 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 Zn2+-binding metalloprotein, and that TPEN effectively strips Zn2+ away from the enzyme. Interestingly, although apo-Cdc25C (Zn2+-deficient) remains fully catalytically active, it is compromised in its ability to dephosphorylate and activate MPF/cdk1. Thus, Zn2+ 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.

Original languageEnglish
Pages (from-to)98-104
Number of pages7
JournalJournal of Cellular Physiology
Volume213
Issue number1
DOIs
Publication statusPublished - Oct 2007
Externally publishedYes

Fingerprint

Zinc
Cell Cycle
Cells
Metalloproteins
Diamines
Micronutrients
Eukaryotic Cells
Chelating Agents
Growth and Development
Transition metals
Metals
Chemical activation
Defects
Enzymes
Growth
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
ethylene

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Zinc regulates the ability of Cdc25C to activate MPF/cdk1. / Sun, Lu; Chai, Yingtao; Hannigan, Robyn; Bhogaraju, Venkata K.; Machaca, Khaled.

In: Journal of Cellular Physiology, Vol. 213, No. 1, 10.2007, p. 98-104.

Research output: Contribution to journalArticle

Sun, Lu ; Chai, Yingtao ; Hannigan, Robyn ; Bhogaraju, Venkata K. ; Machaca, Khaled. / Zinc regulates the ability of Cdc25C to activate MPF/cdk1. In: Journal of Cellular Physiology. 2007 ; Vol. 213, No. 1. pp. 98-104.
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