DNA Damage-Mediated c-Myc Degradation Requires 14-3-3 Sigma
14-3-3σ (sigma) is a gene product upregulated by p53 in response to DNA damage. DNA damage can also alter c-Myc protein levels, but the mechanism by which c-Myc is regulated after DNA damage remains unclear. Here, we discover that the expression of 14-3-3σ is essential to facilitate the degradation of c-Myc in response to DNA damage. 14-3-3σ targets c-Myc for degradation by mediating the interaction between c-Myc and Pin1, which facilitates subsequent ubiquitin-mediated degradation of c-Myc. 14-3-3σ-enhanced c-Myc degradation functionally antagonizes c-Myc-mediated DNA damage (genomic instability) and suppression of p53 transcriptional activity. These results define a novel mechanism for c-Myc inactivation after DNA damage and imply that 14-3-3σ and Pin1 collaborate in response to DNA damage to reduce c-Myc-mediated genomic instability and remove the braking effect of c-Myc on p53 transcriptional activity.
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Document Type: Research Article
Publication date: March 1, 2013
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- World Journal of Cancer Research publishes original articles describing significant new findings in any area related to basic and clinical cancer research. These include studies of cancer related genes, molecules, drugs, cancer cell lines, tumorigenesis, cancer prevention, cancer progression and metastasis, cancer diagnosis, cancer treatment, cancer animal models, human cancer samples as well as cancer patients and all other cancer research related areas.
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