PTPN14 is required for the density-dependent control of YAP1
- Wenqi Wang1,
- Jun Huang2,
- Xin Wang1,
- Jingsong Yuan1,
- Xu Li1,
- Lin Feng1,
- Jae-Il Park1 and
- Junjie Chen1,3
- 1Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;
- 2Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
Abstract
Through an shRNA-mediated loss-of-function screen, we identified PTPN14 as a potential tumor suppressor. PTPN14 interacts with yes-associated protein 1 (YAP1), a member of the hippo signaling pathway. We showed that PTPN14 promotes the nucleus-to-cytoplasm translocation of YAP1 during contact inhibition and thus inhibits YAP1 transactivation activity. Interestingly, PTPN14 protein stability was positively controlled by cell density. We identified the CRL2LRR1 (cullin2 RING ubiquitin ligase complex/leucine-rich repeat protein 1) complex as the E3 ligase that targets PTPN14 for degradation at low cell density. Collectively, these data suggest that PTPN14 acts to suppress cell proliferation by promoting cell density-dependent cytoplasmic translocation of YAP1.
Keywords
Footnotes
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↵3 Corresponding author
E-mail jchen8{at}mdanderson.org
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.192955.112.
- Received March 27, 2012.
- Accepted July 17, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press
