Redox regulation of Cdc25C

Pavel A. Savitsky, Toren Finkel

Research output: Contribution to journalArticle

Abstract

The Cdc25 family of dual specific phosphatases are critical components of cell cycle progression and checkpoint control. Certain stresses such as ultraviolet light stimulate the rapid and selective destruction of Cdc25A protein through a Chk1 protein kinase-dependent pathway. We demonstrate that in contrast to cellular stresses previously examined, hydrogen peroxide exposure affects Cdc25C but not Cdc25A levels. Pharmacological inhibition of Chk1 activity or a mutant of Cdc25C that lacks the Chk1 phosphorylation site still undergoes degradation in response to oxidants. We also demonstrate that in vitro hydrogen peroxide stimulates an intramolecular disulfide bond between the active site cysteine at position 377 and another invariant cysteine at position 330. The in vivo stability of Cdc25C is substantially reduced by the mutation of either of these two cysteine residues. In contrast, a double (C2) mutant of both cysteine 330 and cysteine 377 results in a protein that is more stable than wild type Cdc25C and is resistant to oxidative stress-induced degradation. In addition, the C2 mutant, which is unable to form an intramolecular disulfide bond, has reduced binding to 14-3-3 in vitro and in vivo. These results suggest that oxidative stress may induce cell cycle arrest in part through the degradation of Cdc25C.

Original languageEnglish (US)
Pages (from-to)20535-20540
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number23
DOIs
StatePublished - Jun 7 2002
Externally publishedYes

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Oxidation-Reduction
Cysteine
Oxidative stress
Cell Cycle Checkpoints
Degradation
Disulfides
Hydrogen Peroxide
Oxidative Stress
Cells
Phosphorylation
Ultraviolet Rays
Phosphoric Monoester Hydrolases
Oxidants
Protein Kinases
Catalytic Domain
Proteins
Pharmacology
Mutation
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Savitsky, P. A., & Finkel, T. (2002). Redox regulation of Cdc25C. Journal of Biological Chemistry, 277(23), 20535-20540. https://doi.org/10.1074/jbc.M201589200

Redox regulation of Cdc25C. / Savitsky, Pavel A.; Finkel, Toren.

In: Journal of Biological Chemistry, Vol. 277, No. 23, 07.06.2002, p. 20535-20540.

Research output: Contribution to journalArticle

Savitsky, PA & Finkel, T 2002, 'Redox regulation of Cdc25C', Journal of Biological Chemistry, vol. 277, no. 23, pp. 20535-20540. https://doi.org/10.1074/jbc.M201589200
Savitsky, Pavel A. ; Finkel, Toren. / Redox regulation of Cdc25C. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 23. pp. 20535-20540.
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