Volume 23, No 5, May 2013
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 23 Issue 5, May 2013: 620-634
ORIGINAL ARTICLES
Def defines a conserved nucleolar pathway that leads p53 to proteasome-independent degradation
Ting Tao1,*, Hui Shi1,*, Yihong Guan1, Delai Huang1, Ye Chen1, David P Lane 3, Jun Chen2 and Jinrong Peng1
1Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, Ministry of Education, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, Zhejiang 310058, China
2College of Life Sciences, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou, Zhejiang 310058, China
3p53 Laboratory, Agency for Science and Technology Research, 8A Biomedical Grove, #6-06, Immunos, Singapore 138648
Correspondence: Jinrong Peng, Jun Chen, David P Lane(pengjr@zju.edu.cn; chenjun2009@zju.edu.cn; dplane@p53Lab.a-star.edu.sg)
p53 protein turnover through the ubiquitination pathway is a vital mechanism in the regulation of its transcriptional activity; however, little is known about p53 turnover through proteasome-independent pathway(s). The digestive organ expansion factor (Def) protein is essential for the development of digestive organs. In zebrafish, loss of function of def selectively upregulates the expression of p53 response genes, which raises a question as to what is the relationship between Def and p53. We report here that Def is a nucleolar protein and that loss of function of def leads to the upregulation of p53 protein, which surprisingly accumulates in the nucleoli. Our extensive studies have demonstrated that Def can mediate the degradation of p53 protein and that this process is independent of the proteasome pathway, but dependent on the activity of Calpain3, a cysteine protease. Our findings define a novel nucleolar pathway that regulates the turnover function of p53, which will advance our understanding of p53's role in organogenesis and tumorigenesis.
Cell Research (2013) 23:620–634. doi:10.1038/cr.2013.16; published online 29 January 2013
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