SIRT1 increases YAP- and MKK3-dependent p38 phosphorylation in mouse liver and human hepatocellular carcinoma.
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.
['Wang|Yulan|Y|', 'Cui|Ran|R|', 'Zhang|Xiao|X|', 'Qiao|Yongxia|Y|', 'Liu|Xiangfan|X|', 'Chang|Yefei|Y|', 'Yu|Yongchun|Y|', 'Sun|Fenyong|F|', 'Wang|Jiayi|J|']
D048868:Adaptor Proteins, Signal Transducing D000818:Animals D006528:Carcinoma, Hepatocellular D018797:Cell Cycle Proteins D004195:Disease Models, Animal D006801:Humans D008099:Liver D008113:Liver Neoplasms D048371:MAP Kinase Kinase 3 D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D008822:Mice, Transgenic D010750:Phosphoproteins D010766:Phosphorylation D056564:Sirtuin 1 D016019:Survival Analysis D014157:Transcription Factors D000091102:YAP-Signaling Proteins D048051:p38 Mitogen-Activated Protein Kinases
liver cancer RNA polymerase II cell proliferation promoter survival