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Title: PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site

Highlights: • PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at Thr{sup 387}. • Overexpression of PHLPP1 sensitizes contact inhibition. • Tumor cells with suppressed PHLPP1 expression are refractory to apoptosis and highly proliferative. • Loss or down-regulation of PHLPP1 may drive tumor development and progression. - Abstract: Contact inhibition has been largely elusive despite that a loss of contact inhibition is a critical event for cancer development and progression. Here, we report that PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr{sup 387} of Mst1. Yap1 was localized predominantly in the nucleus but marginally in the cytoplasm in HeLa cells under sparse conditions, whereas the functional protein was more directed to sequestration in the cytoplasm under dense environments. Furthermore, loss of PHLPP1 resulted in a failure of the apoptotic control. It is interesting that down-regulated expression of PHLPP1 appears to mimic the loss of contact inhibition, a hallmark of cancer.
Authors:
;  [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [2] ;  [1] ;  [2]
  1. Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon (Korea, Republic of)
  2. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416245
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 443; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CYTOPLASM; FAILURES; HELA CELLS; INHIBITION; LOSSES; NEOPLASMS; PROTEINS; SENSITIZERS