title: USP1 regulates AKT phosphorylation by modulating the stability of PHLPP1 in lung cancer cells.
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.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Xinxiang Medical College, Weihui 453100, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhiqiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Qinghui
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yongqiang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Jian
authors.forename: Zhao
authors.initials: Z
authors.lastname: Xin
authors.forename: Ma
authors.initials: M
authors.lastname: Haiying
authors.forename: Guo
authors.initials: G
authors.lastname: Yuepeng
mesh_terms: D029681:Arabidopsis Proteins; D016923:Cell Death; D045744:Cell Line, Tumor; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D064570:Ubiquitin-Specific Proteases; D054875:Ubiquitination
chemical_list: D029681:Arabidopsis Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases; D010450:Endopeptidases; C579228:USP1 protein, human; D064570:Ubiquitin-Specific Proteases