Abstract
The Cdc25A phosphatase positively regulates cell-cycle transitions, is degraded by the proteosome throughout interphase and in response to stress, and is overproduced in human cancers. The kinases targeting Cdc25A for proteolysis during early cell-cycle phases have not been identified, and mechanistic insight into the cause of Cdc25A overproduction in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3β (GSK-3β) phosphorylates Cdc25A to promote its proteolysis in early cell-cycle phases. Phosphorylation by GSK-3β requires priming of Cdc25A, and this can be catalyzed by polo-like kinase 3 (Plk-3). Importantly, a strong correlation between Cdc25A overproduction and GSK-3β inactivation was observed in human tumor tissues, indicating that GSK-3β inactivation may account for Cdc25A overproduction in a subset of human tumors.
Original language | English (US) |
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Pages (from-to) | 36-47 |
Number of pages | 12 |
Journal | Cancer cell |
Volume | 13 |
Issue number | 1 |
DOIs | |
State | Published - Jan 8 2008 |
Keywords
- CELLCYCLE
- SIGNALING
ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
MD Anderson CCSG core facilities
- Flow Cytometry and Cellular Imaging Facility