| Autor: |
Charles Spruck, Martin Widschwendter, James Wohlschlegel, Ajay A. Vashisht, Kathleen Klotz-Noack, Weijian Jiang, Dahui Sun, YingMeei Tan |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6505728 |
| Popis: |
Cyclin E1 regulates the initiation of S-phase in cellular division. However, in many cancers, cyclin E1 is aberrantly overexpressed and this molecular phenotype correlates with increased tumor aggressiveness and poor patient survival. The molecular cause(s) of cyclin E1 abnormalities in cancers is poorly understood. Here, we show that cyclin E1 overexpression in cancer is promoted by dysregulation of the protein phosphatase PP2A-B55β. PP2A-B55β targets the N- and C-terminal phosphodegrons of cyclin E1 for dephosphorylation, thus protecting it from degradation mediated by the SCFFbxw7 ubiquitin ligase. Augmented B55β expression stabilizes cyclin E1 and promotes its overexpression in cancer-derived cell lines and breast tumors. Conversely, B55β ablation enforces the degradation of cyclin E1 and inhibits cancer cell proliferation in vitro and tumor formation in vivo. Therefore, PP2A-B55β promotes cyclin E1 overexpression by antagonizing its degradation and its inhibition could represent a therapeutic mechanism for abrogating cyclin E1 function in cancers. Cancer Res; 74(7); 2006–14. ©2014 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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