title: Ubiquitin-specific peptidase USP22 negatively regulates the STAT signaling pathway by deubiquitinating SIRT1.
abstract: OBJECTIVE
  The ubiquitin-specific peptidase USP22 mediates various cellular and organismal processes, such as cell growth, apoptosis, and tumor malignancy. However, the molecular mechanisms that regulate USP22 activity remain poorly understood. Here we identify STAT3 as a new USP22 interactor.
  
  
  METHODS
  · We used western blotting and RT-PCR to measure key protein, acetylated STAT3, and mRNA levels in HEK293 and colorectal cancer cell lines transfected with expression plasmids or specific siRNAs. Co-immunoprecipitation was used to demonstrate protein-protein interaction and protein complex composition.
  
  
  RESULTS
  USP22 overexpression down-regulated STAT3 acetylation by deubiquitinating SIRT1. The three proteins were found to be present in a single protein complex. SiRNA-mediated depletion of endogenous USP22 resulted in SIRT1 destabilization and elevated STAT3 acetylation. Consistent with this finding, USP22 also down-regulated the expression of two known STAT3 target genes, MMP9 and TWIST.
  
  
  CONCLUSIONS
  We show that USP22 is a new regulator of the SIRT1-STAT3 signaling pathway and report a new mechanistic explanation for cross talk between USP22 and the SIRT1-STAT pathways.
authors: Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing, China.
authors: Ning
authors: N
authors: Ao
authors: Yanyan
authors: Y
authors: Liu
authors: Hailiang
authors: H
authors: Feng
authors: Xiaocui
authors: X
authors: Bian
authors: Zhanwen
authors: Z
authors: Li
authors: Bei
authors: B
authors: Gu
authors: Xiaomei
authors: X
authors: Zhao
authors: Yuqin
authors: Y
authors: Liu
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D054875:Ubiquitination
chemical_list: D050796:STAT3 Transcription Factor; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1