Nature Cell Biology
- 8, 1359 - 1368 (2006)
Published online: 19 November 2006; | doi:10.1038/ncb1501
Tyrosine phosphorylation controls PCNA function through protein stabilityShao-Chun Wang1, 8, Yusuke Nakajima1, 2, 8, Yung-Luen Yu1, 8, Weiya Xia1, Chun-Te Chen1, 3, Cheng-Chieh Yang1, 3, Eric W. McIntush4, Long-Yuan Li1, 5, David H. Hawke6, Ryuji Kobayashi6 & Mien-Chie Hung1, 3, 71
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. 2
Current address: Oral and Maxillofacial Surgery, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8549, Japan. 3
Graduate School of Biomedical Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. 4
Bethyl Laboratories, Inc., 25043 W. FM1097, Montgomery, TX 77356, USA. 5
Current address: Center for Molecular Medicine, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung 404, Taiwan. 6
Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. 7
Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan. 8
These authors contributed equally to the work.
Correspondence should be addressed to Mien-Chie Hung mhung@mdanderson.org The proliferating cell nuclear antigen (PCNA) is an essential protein for DNA replication and damage repair. How its function is controlled remains an important question. Here, we show that the chromatin-bound PCNA protein is phosphorylated on Tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of EGF receptor (EGFR) in the nucleus. Phosphorylation on Tyr 211 by EGFR stabilizes chromatin-bound PCNA protein and associated functions. Consistently, increased PCNA Tyr 211 phosphorylation coincides with pronounced cell proliferation, and is better correlated with poor survival of breast cancer patients, as well as nuclear EGFR in tumours, than is the total PCNA level. These results identify a novel nuclear mechanism linking tyrosine kinase receptor function with the regulation of the PCNA sliding clamp.
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