期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 20, 页码 18251-18260出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.208587
关键词
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资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Ministry of Health, Labor, and Welfare Japan
- National Institute of Biomedical Innovation
- New Energy and Industrial Technology Development Organization
- Hayashi Memorial Foundation for Female Natural Scientists
- Sagawa Foundation for Promoting Cancer Research
- Takeda Science Foundation
- Kobayashi Foundation for Cancer Research
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Grants-in-Aid for Scientific Research [23501271, 23300365] Funding Source: KAKEN
The common polymorphism of p53 at codon 72, either encoding proline or arginine, has drawn attention as a genetic factor associated with clinical outcome or cancer risk for the last 2 decades. We now show that these two polymorphic variants differ in protein structure, especially within the N-terminal region and, as a consequence, differ in post-translational modification at the N terminus. The arginine form (p53-72R) shows significantly enhanced phosphorylation at Ser-6 and Ser-20 compared with the proline form (p53-72P). We also show diminished Mdm2-mediated degradation of p53-72R compared with p53-72P, which is at least partly brought about by higher levels of phosphorylation at Ser-20 in p53-72R. Furthermore, enhanced p21 expression in p53-72R-expressing cells, which is dependent on phosphorylation at Ser-6, was demonstrated. Differential p21 expression between the variants was also observed upon activation of TGF-beta signaling. Collectively, we demonstrate a novel molecular difference and simultaneously suggest a difference in the tumor-suppressing function of the variants.
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