title: The tumor suppressor protein menin inhibits NF-κB-mediated transactivation through recruitment of Sirt1 in hepatocellular carcinoma.
abstract: Oncogenic activation of the NF-κB signaling pathway is common in hepatocellular carcinoma (HCC). However, the molecular mechanisms remain largely unexplored. Previous studies have demonstrated that menin, a tumor suppressor protein, could interact with NF-κB protein and repress p65-mediated transcriptional activation. In the present study, we found that expression of menin was frequently down-regulated in HCC tissues and cells. Furthermore, menin could repress p65 acetylation through recruitment of Sirt1, an enzyme that deacetylases p65 in lysine 310 (K310). Indeed, Sirt1 inhibitor or its specific small interfering RNA abolished the inhibitory roles of menin. Together, these observations suggest that the interaction between menin and Sirt1 is required for the tumor suppressor function of menin in HCC.
authors.affiliation: Department of Oncology, Chongming Branch of Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. dinggangcm@gmail.com
authors.forename: Ding
authors.initials: D
authors.lastname: Gang
authors.forename: Hua
authors.initials: H
authors.lastname: Hongwei
authors.forename: Liu
authors.initials: L
authors.lastname: Hedai
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ming
authors.forename: Huang
authors.initials: H
authors.lastname: Qian
authors.forename: Liao
authors.initials: L
authors.lastname: Zhijun
mesh_terms: D000107:Acetylation; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C105373:MEN1 protein, human; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051996:Transcription Factor RelA; C447939:SIRT1 protein, human; D056564:Sirtuin 1