title: RBB, a novel transcription repressor, represses the transcription of HDM2 oncogene.
abstract: The p53 tumor suppressor is important in many aspects of cell biology. Tight regulation of p53 is thus imperative for maintaining cell homeostasis and preventing tumorigenesis. The stabilization and activity of p53 is primarily regulated by MDM2, which is encoded for by HDM2. However, how the expression and activity of MDM2 is regulated remains largely unknown. Here, we report a novel BTB and BEN domains-containing protein, RBB. We demonstrated that RBB is a novel transcriptional repressor binding specific DNA motif via a homodimer and interacting with the nucleosome remodeling and deacetylase (NuRD) complex. Genome wide transcription target analysis by ChIP sequencing revealed that RBB represses the transcription of a series of functionally important genes including HDM2. We showed that RBB recruits the NuRD complex to the internal promoter of HDM2 and inhibits the expression of MDM2 protein, leading to subsequent stabilization of tumor suppressor p53. Significantly, we showed that RBB suppresses cell proliferation and sensitizes cells to DNA damage-induced apoptosis. Our data indicate that RBB is a novel transcriptional repressor and an important regulator of p53 pathway.
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China. chenghaoxuan@bjmu.edu.cn
authors.forename: C
authors.initials: C
authors.lastname: Xuan
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.forename: Y
authors.initials: Y
authors.lastname: Duan
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Shi
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Shan
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
authors.forename: Y
authors.initials: Y
authors.lastname: Shang
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D051379:Mice; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D002843:Chromatin; D006657:Histones; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004247:DNA; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex