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

作者：Zhang Zhiqiang; Yang Qinghui; Zhang Yongqiang; Zhang Jian; Zhao Xin; Ma Haiying; Guo Yuepeng^*

来源：Journal of Cancer Research and Clinical Oncology, 2012, 138(7): 1231-1238.

DOI：10.1007/s00432-012-1193-3

• AKT phosphorylation deubiquitination
• Lung cancer
• USP1
• PHLPP1

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.
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.
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.

• 出版日期2012-7
• 单位新乡医学院