title: SIRT1 increases YAP- and MKK3-dependent p38 phosphorylation in mouse liver and human hepatocellular carcinoma.
abstract: Both oncoprotein and tumor-suppressor activity have been reported for SIRTUIN1 (SIRT1) and p38 in many types of cancer. The effect of SIRT1 on p38 phosphorylation (p-p38) remains controversial and may be organ- and cell-specific. We found that SIRT1 is essential for maintaining liver size and weight in mice. SIRT1 levels were elevated in human HCC compared to adjacent normal liver tissue, and its expression correlated positively with p-p38 levels. Additionally, SIRT1-activated p38 increased liver cancer malignancy. SIRT1 increased phosphorylation and nuclear accumulation of p38, possibly by increasing MKK3 expression. SIRT1 also induced YAP expression, which in turn increased MKK3 transcription. Positive correlations between SIRT1, YAP, MKK3, and p-p38 levels indicate that blocking their activity may prove helpful in treating HCC.
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Cui
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Faculty of Medical Laboratory Science, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiangfan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory Medicine, Third People's Hospital of Yunnan Province, Kunming, 650011, Yunnan Province, China.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai TCM University, Shanghai, 200071, China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.|Advanced Institute of Translational Medicine, Tongji University, Shanghai, 200092, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D048371:MAP Kinase Kinase 3 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D056564:Sirtuin 1 / Q000378:metabolism*; D016019:Survival Analysis; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C486223:Yap1 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; C482530:MAP2K3 protein, human; C482531:Map2k3 protein, mouse; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: RNA polymerase II; cell proliferation; liver cancer; promoter; survival
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