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J Cancer Res Clin Oncol. 2012 Jul;138(7):1231-8. doi: 10.1007/s00432-012-1193-3. Epub 2012 Mar 20.

USP1 regulates AKT phosphorylation by modulating the stability of PHLPP1 in lung cancer cells.

Author information

1
Department of Respiratory Medicine, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, China.

Abstract

BACKGROUND:

Hyperactivation of phosphatidylinositol 3-kinase/Akt signaling is commonly associated with human tumors including lung cancers. PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1), which terminates Akt signaling by directly dephosphorylating and inactivating Akt, has been identified as a tumor suppressor. The protein level of PHLPP1 is regulated by E3 ligase beta-TRCP, however, the deubiquitinase for PHLPP1 is still not known.

METHODS:

The mRNA levels of USP1 and PHLPP1 in lung cancer cells and tissues were determined by real-time PCR. The half-life of PHLPP1 was detected by CHX assay. The interaction between USP1 and PHLPP1 was examined by immunoprecipitation and GST pull-down assay.

RESULTS:

Both USP1 and PHLPP1 are low expressed in lung cancer cells and tissues and silencing of USP1 by RNA interference significantly decreased the half-life of PHLPP1, which in turn amplified Akt1 phosphorylation. Our data identified a novel USP1-PHLPP1-Akt signaling axis, and decreased USP1 level in lung cancer cells may play an important role in lung cancer progress.

PMID:
22426999
DOI:
10.1007/s00432-012-1193-3
[Indexed for MEDLINE]

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