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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your
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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS A NOVEL CDC25A/DYRK2 REGULATORY SWITCH MODULATES CELL CYCLE AND
SURVIVAL Article Open access 06 August 2021 CDC7-INDEPENDENT G1/S TRANSITION REVEALED BY TARGETED PROTEIN DEGRADATION Article 04 May 2022 THE E3 UBIQUITIN LIGASE HECTD1 CONTRIBUTES TO CELL
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We thank CL Attwooll and AP Bracken for critically reading the manuscript. Work in the authors' laboratory is supported by grants from AIRC, FIRC and Telethon. AUTHOR INFORMATION
Author notes * Luca Busino and Massimo Chiesa: Both these authors contributed equally to this work AUTHORS AND AFFILIATIONS * European Institute of Oncology, 435 Via Ripamonti, Milan, 20141,
Italy Luca Busino, Massimo Chiesa, Giulio F Draetta & Maddalena Donzelli Authors * Luca Busino View author publications You can also search for this author inPubMed Google Scholar *
Massimo Chiesa View author publications You can also search for this author inPubMed Google Scholar * Giulio F Draetta View author publications You can also search for this author inPubMed
Google Scholar * Maddalena Donzelli View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Maddalena Donzelli. RIGHTS AND
PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Busino, L., Chiesa, M., Draetta, G. _et al._ Cdc25A phosphatase: combinatorial phosphorylation, ubiquitylation and
proteolysis. _Oncogene_ 23, 2050–2056 (2004). https://doi.org/10.1038/sj.onc.1207394 Download citation * Published: 15 March 2004 * Issue Date: 15 March 2004 * DOI:
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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Cdc25A * APC/C * SCF * check points