Cdc25A phosphatase: Combinatorial phosphorylation, ubiquitylation and proteolysis

Luca Busino, Massimo Chiesa, Giulio F. Draetta, Maddalena Donzelli

Research output: Contribution to journalArticle

Abstract

In eukaryotic cells, control mechanisms of cell-cycle progression have evolved to accurately monitor the integrity of genetic information to be transferred to the progeny. Cdc25A phosphatase is an essential activator of cell-cycle progression and is targeted by checkpoint signals. Ubiquitylation regulates Cdc25A activity through fine tuning of its protein levels. Two different ubiquitin ligases (APC/C and SCF complex) are involved in Cdc25A turnover. While APC/C is involved in regulating Cdc25A at the exit of mitosis, SCF regulates the abundance of Cdc25A in S phase and G2. In response to DNA damage or to stalled replication, the activation of the ATM and ATR protein kinases leads to Chk1 and Chk2 activation and to Cdc25A hyperphosphorylation. These events stimulate SCF-mediated ubiquitylation of Cdc25A and its proteolysis. This contributes to delaying cell-cycle progression, thereby preventing genomic instability. Based on recent findings, we discuss the role of Cdc25A ubiquitylation and degradation in cell-cycle progression and in response to DNA damage. Moreover, we discuss the role of phosphorylation at multiple sites in triggering ubiquitylation signals.

Original languageEnglish
Pages (from-to)2050-2056
Number of pages7
JournalOncogene
Volume23
Issue number11 REV. ISS. 1
DOIs
Publication statusPublished - Mar 15 2004

Keywords

  • APC/C
  • Cdc25A
  • Checkpoints
  • SCF

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Cdc25A phosphatase: Combinatorial phosphorylation, ubiquitylation and proteolysis'. Together they form a unique fingerprint.

  • Cite this

    Busino, L., Chiesa, M., Draetta, G. F., & Donzelli, M. (2004). Cdc25A phosphatase: Combinatorial phosphorylation, ubiquitylation and proteolysis. Oncogene, 23(11 REV. ISS. 1), 2050-2056. https://doi.org/10.1038/sj.onc.1207394