التفاصيل البيبلوغرافية
| العنوان: |
MTA1 Coregulator Regulates p53 Stability and Function. |
| المؤلفون: |
Da-Qiang Li1, Reddy, Sirigiri Divijendra Natha1, Pakala, Suresh B.1, Xifeng Wu2, Yanping Zhang3, Rayala, Suresh K.1, Kumar, Rakesh1 bcmrxk@gwumc.edu |
| المصدر: |
Journal of Biological Chemistry. 12/11/2009, Vol. 284 Issue 50, p34545-34552. 8p. |
| مصطلحات موضوعية: |
*P53 protein, *DNA damage, *DOUBLE-stranded RNA, *NUCLEOTIDES, *DNA repair, *CANCER cells |
| مستخلص: |
Although metastasis-associated protein 1 (MTA1) has recently been shown as a DNA damage responsive protein, the underlying mechanism for its role in DNA double-strand break (DSB) repair remains unknown. Here, we show that MTA1 controls p53 stability through inhibiting its ubiquitination by E3 ubiquitin ligases mouse double minute 2 (Mdm2) and constitutive photomorphogenic protein 1 (COP1). The underlying mechanisms involve the ability ofMTA1 to compete with COP! to bind to p53 and/or to destabilize COP1 and Mdm2. Consequently, MTA1 regulates the p53-dependent transcription of p53R2, a direct p53 target gene for supplying nucleotides to repair damaged DNA. Depletion of MTA1 impairs p53-dependent p53R2 transcription and compromises DNA repair. Interestingly, these events could be reversed by MTA1 reintroduction, indicating that MTA1 interjects into the p53-dependent DNA repair. Given the fact that MTA1 is widely up-regulated in human cancers, these findings in conjunction with our earlier finding of a crucial role ofMTA1 in DSB repair suggest an inherent role of the MTA1-p53-p53R2 pathway in DNA damage response in cancer cells. [ABSTRACT FROM AUTHOR] |
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