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.
BACKGROUND: Hyperactivation of phosphatidylinositol 3-kinase/Akt signaling is commonly associated with humantumors 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.
Authors: Sebastian M B Nijman; Tony T Huang; Annette M G Dirac; Thijn R Brummelkamp; Ron M Kerkhoven; Alan D D'Andrea; René Bernards Journal: Mol Cell Date: 2005-02-04 Impact factor: 17.970
Authors: Tony T Huang; Sebastian M B Nijman; Kanchan D Mirchandani; Paul J Galardy; Martin A Cohn; Wilhelm Haas; Steven P Gygi; Hidde L Ploegh; René Bernards; Alan D D'Andrea Journal: Nat Cell Biol Date: 2006-03-12 Impact factor: 28.824
Authors: Urszula L McClurg; Nay C T H Chit; Mahsa Azizyan; Joanne Edwards; Arash Nabbi; Karl T Riabowol; Sirintra Nakjang; Stuart R McCracken; Craig N Robson Journal: Oncogene Date: 2018-05-14 Impact factor: 9.867