SCIENCE@home

PEPD is a pivotal regulator of p53 tumor suppressor

Lu Yang,Yun Li,Arup Bhattacharya,Yuesheng Zhang

Published 2017 in Nature Communications

ABSTRACT

Abstractp53 tumor suppressor responds to various cellular stresses and regulates cell fate. Here, we show that peptidase D (PEPD) binds and suppresses over half of nuclear and cytoplasmic p53 under normal conditions, independent of its enzymatic activity. Eliminating PEPD causes cell death and tumor regression due to p53 activation. PEPD binds to the proline-rich domain in p53, which inhibits phosphorylation of nuclear p53 and MDM2-mediated mitochondrial translocation of nuclear and cytoplasmic p53. However, the PEPD-p53 complex is critical for p53 response to stress, as stress signals doxorubicin and H2O2 each must free p53 from PEPD in order to achieve robust p53 activation, which is mediated by reactive oxygen species. Thus, PEPD stores p53 for the stress response, but this also renders cells dependent on PEPD for survival, as it suppresses p53. This finding provides further understanding of p53 regulation and may have significant implications for the treatment of cancer and other diseases.p53 is a pivotal tumour suppressor that is activated by various cellular stress inducers. Here, the authors show that peptidase D (PEPD) promotes the growth of cancer cells by suppressing p53 and that the complex PEPD-p53 is critical for robust p53 activation in response to stress signals.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-60 of 60 references · Page 1 of 1

CITED BY

Showing 1-28 of 28 citing papers · Page 1 of 1