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Genes Dev. 2012 Sep 1;26(17):1959-71. doi: 10.1101/gad.192955.112.

PTPN14 is required for the density-dependent control of YAP1.

Author information

1
Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

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 CRL2(LRR1) (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.

PMID:
22948661
PMCID:
PMC3435498
DOI:
10.1101/gad.192955.112
[Indexed for MEDLINE]
Free PMC Article

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