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- Title
Characterization of a new mouse p53 variant: lossof- function and gain-of-function.
- Authors
James Yi-Hsin Chan; Ying-Chuan Chen; Shu-Ting Liu; Wei-Yuan Chou; Ching-Liang Ho; Shih-Ming Huang
- Abstract
Background p53 is a major tumor suppressor that is inactivated in over 50% of human cancer types through either mutation or inactivating interactions with viral or cellular proteins. The uncertainties around the link between p53 status, therapeutic response, and outcome in cancer suggest that additional factors may be involved. p53 isoforms that are generated via the alternative splicing pathway may be promising candidates for further investigation. Result In this study, we report one new p53 protein with two internally deleted regions, resulting in one deleted amino acid fragment (from amino acid residues 42 to 89) and one reading frameshift region (from amino acid residues 90-120) compared to wild-type p53. The functional status of the new p53 protein, which has a defect in its proline-rich and N-terminal DNAbinding domains, was characterized as possessing an intact conformation, exhibiting no transactivation activity, exerting a dominant-negative effect and an interacting with a coactivator with an arginine methyltransferase activity. Conclusion Taken together, our findings provide valuable information about the structure and function of p53 for the regulation of transactivation activity and cellular protein-protein interactions. Furthermore, natural p53 isoforms will help us understand the functional roles of the p53 family and potential therapeutics for p53-dependent cancers.
- Subjects
TUMORS; CLINICAL medicine; AMINO acids; PROTEINS; THERAPEUTICS
- Publication
Journal of Biomedical Science, 2014, Vol 21, Issue 1, p1
- ISSN
1021-7770
- Publication type
Article
- DOI
10.1186/1423-0127-21-40