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- W4361822315 abstract "<div>Abstract<p>Constitutive photomorphogenic 1 (COP1) is a p53-targeting E3 ubiquitin ligase that is downregulated by DNA damage through mechanisms that remain obscure. Here, we report that COP1 is not downregulated following DNA damage in 14-3-3σ null cells, implicating 14-3-3σ as a critical regulator in the response of COP1 to DNA damage. We also identified that 14-3-3σ, a p53 target gene product, interacted with COP1 and controlled COP1 protein stability after DNA damage. Mechanistic studies revealed that 14-3-3σ enhanced COP1 self-ubiquitination, thereby preventing COP1-mediated p53 ubiquitination, degradation, and transcriptional repression. In addition, we found that COP1 expression promoted cell proliferation, cell transformation, and tumor progression, manifesting its role in cancer promotion, whereas 14-3-3σ negatively regulated COP1 function and prevented tumor growth in a mouse xenograft model of human cancer. Immunohistochemical analysis of clinical breast and pancreatic cancer specimens demonstrated that COP1 protein levels were inversely correlated with 14-3-3σ protein levels. Together, our findings define a mechanism for posttranslational regulation of COP1 after DNA damage that can explain the correlation between COP1 overexpression and 14-3-3σ downregulation during tumorigenesis. <i>Cancer Res; 71(3); 884–94. ©2010 AACR</i>.</p></div>" @default.
- W4361822315 created "2023-04-05" @default.
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- W4361822315 date "2023-03-30" @default.
- W4361822315 modified "2023-10-17" @default.
- W4361822315 title "Data from 14-3-3σ Exerts Tumor-Suppressor Activity Mediated by Regulation of COP1 Stability" @default.
- W4361822315 doi "https://doi.org/10.1158/0008-5472.c.6502856.v1" @default.
- W4361822315 hasPublicationYear "2023" @default.
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