Journal article

c-Abl Phosphorylates E6AP and Regulates Its E3 Ubiquitin Ligase Activity

Ai-Leen Chan, Tamar Grossman, Valentina Zuckerman, Dafne Campigli Di Giammartino, Ofra Moshe, Martin Scheffner, Brendon Monahan, Pat Pilling, Yong-Hui Jiang, Sue Haupt, Ora Schueler-Furman, Ygal Haupt

BIOCHEMISTRY | AMER CHEMICAL SOC | Published : 2013

Abstract

In human papillomavirus (HPV)-infected cells, the p53 tumor suppressor is tightly regulated by the HPV-E6-E6AP complex, which promotes it for proteasomal degradation. We previously demonstrated that c-Abl tyrosine kinase protects p53 from HPV-E6-E6AP complex-mediated ubiquitination and degradation under stress conditions. However, the underlying mechanism was not defined. In this study, we explored the possibility that c-Abl targets E6AP and thereby protects p53. We demonstrated that c-Abl interacts with and phosphorylates E6AP. We determined that the E3 ligase activity of E6AP is impaired in response to phosphorylation by c-Abl. We mapped the phosphorylation site to tyrosine 636 within the ..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Funding Acknowledgements

This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia to Y.H. (509196, 1026988, and 1026990), a grant from the Cancer Council Victoria, and the VESKI award. Y.H. is an NHMRC Senior Research Fellow (628426).