title: De-regulation of the RBBP6 isoform 3/DWNN in human cancers.
abstract: Retinoblastoma binding protein 6 (RBBP6) is a nuclear protein, previously implicated in the regulation of cell cycle and apoptosis. The human RBBP6 gene codes for three protein isoforms and isoform 3 consists of the domain with no name domain only whilst the other two isoforms, 1 and 2 comprise of additional zinc, RING, retinoblastoma and p53 binding domains. In this study, the localization of RBBP6 using RBBP6 variant 3 mRNA-specific probe was performed to investigate the expression levels of the gene in different tumours and find a link between RBBP6 and human carcinogenesis. Using FISH, real-time PCR and Western blotting analysis our results show that RBBP6 isoform 3 is down-regulated in human cancers. RBBP6 isoform 3 knock-down resulted in reduced G2/M cell cycle arrest whilst its over-expression resulted in increased G2/M cell cycle arrest using propidium iodide DNA staining. The results further demonstrate that the RBBP6 isoform 3 may be the cell cycle regulator and involved in mitotic apoptosis not the isoform 1 as previously reported for mice. In conclusion, these findings suggest that RBBP6 isoform 3 is a cell cycle regulator and may be de-regulated in carcinogenesis.
authors.affiliation: College of Agriculture and Environmental Science, University of South Africa, Florida Campus, Johannesburg, South Africa.
authors.forename: Zukile
authors.initials: Z
authors.lastname: Mbita
authors.forename: Mervin
authors.initials: M
authors.lastname: Meyer
authors.forename: Amanda
authors.initials: A
authors.lastname: Skepu
authors.forename: Margot
authors.initials: M
authors.lastname: Hosie
authors.forename: Jasper
authors.initials: J
authors.lastname: Rees
authors.forename: Zodwa
authors.initials: Z
authors.lastname: Dlamini
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; C098584:RBBP6 protein, human; D044767:Ubiquitin-Protein Ligases