Characterization of a new mouse p53 variant: loss-of-function and gain-of-function

Journal of Biomedical Science

Shih-Ming Huang²  Ching-Liang Ho³  Wei-Yuan Chou²  Shu-Ting Liu²  Ying-Chuan Chen²  James Yi-Hsin Chan¹ 

[1] Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan;Department of Medicine, Division of Hematology/Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan

关键词: Dominant negative effect;    Conformation;    Transactivation;    p21;    p53;   

Others  :  817619
DOI  :  10.1186/1423-0127-21-40

 received in 2014-01-03, accepted in 2014-05-05,  发布年份 2014

【 摘 要 】

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 frame-shift 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 DNA-binding 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.

【 授权许可】

   
2014 Chan et al.; licensee BioMed Central Ltd.

【 图 表 】

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