PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site

Journal Article · Fri Jan 24 04:00:00 EST 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.12.129· OSTI ID:22416245

Jung, Sujin; Kang, Jeong Gu ^[1]; Lee, Ju Hee ^[1]; Song, Kyoung Jin ^[1]; Ko, Jeong-Heon ^[1]; Kim, Yong-Sam ^[1]

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1. Targeted Gene Regulation Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Deajeon (Korea, Republic of)

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.

• OSTI ID: 22416245
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 443; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CYTOPLASM
FAILURES
HELA CELLS
INHIBITION
LOSSES
NEOPLASMS
PROTEINS
SENSITIZERS