title: MDM2-MOF-H4K16ac axis contributes to tumorigenesis induced by Notch.
abstract: Identification of the epigenetic mechanisms involved in the transmission of Notch signaling is useful for personalized medicine. We observed that aberrantly high levels of Notch activity resulted in H4K16ac downregulation in hepatocellular carcinoma and breast cancer cell lines and tissues. This downregulated acetylation was a consequence of increased male on the first degradation following the upregulation of full-length murine double minute 2 in different cancer types. We observed that increases in male on the first could attenuate heterogeneity induced by aberrantly high levels of Notch activity. Our results provide new insights into the analysis and treatment of Notch-induced hepatocellular carcinoma and breast cancer.
authors.affiliation: College of Life Sciences, Hebei United University, Tangshan, China; Central Laboratory, Cancer Institute, Tangshan People's Hospital, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhao-Bin
authors.initials: ZB
authors.lastname: Xing
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.forename: Yan-Kun
authors.initials: YK
authors.lastname: Liu
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Li
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Li
authors.forename: Ya-Qi
authors.initials: YQ
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Wan-Ning
authors.initials: WN
authors.lastname: Hu
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000107:Acetylation; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D006657:Histones; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: MDM2; MOF; Notch; acetylation; histone modification