Ubiquitin-Specific Peptidase USP22 Negatively Regulates the STAT Signaling Pathway by Deubiquitinating SIRT1
| Autor: | Yuqin Liu, Xiao-Mei Zhao, Ning Ao, Bei Gu, Zhanwen Li, Yanyan Liu, Xiaocui Bian, Hailiang Feng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
STAT3 Transcription Factor
Small interfering RNA Physiology Blotting Western USP22 lcsh:Physiology STAT3 lcsh:Biochemistry SIRT1 Sirtuin 1 Ubiquitin RNA interference Cell Line Tumor Humans lcsh:QD415-436 Deubiquitinating Regulation of gene expression biology lcsh:QP1-981 Reverse Transcriptase Polymerase Chain Reaction Chemistry HEK 293 cells Ubiquitination Acetylation HCT116 Cells Cell biology Gene Expression Regulation Neoplastic HEK293 Cells Microscopy Fluorescence biology.protein Cancer research RNA Interference Thiolester Hydrolases Signal transduction HT29 Cells Ubiquitin Thiolesterase Protein Binding Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 33, Iss 6, Pp 1863-1875 (2014) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: 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. Conclusion: 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. |
| Databáze: | OpenAIRE |
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