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Molecular and Cellular Biochemistry

, Volume 362, Issue 1–2, pp 249–262 | Cite as

De-regulation of the RBBP6 isoform 3/DWNN in human cancers

  • Zukile Mbita
  • Mervin Meyer
  • Amanda Skepu
  • Margot Hosie
  • Jasper Rees
  • Zodwa Dlamini
Article

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.

Keywords

RBBP6 isoform 3 Cell cycle Apoptosis Human cancers and FISH 

Notes

Acknowledgments

We are grateful to the National Research Foundation (South Africa), the Council for Scientific and Industrial Research (CSIR) and the University of the Witwatersrand for funding.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Zukile Mbita
    • 1
  • Mervin Meyer
    • 2
  • Amanda Skepu
    • 3
  • Margot Hosie
    • 4
  • Jasper Rees
    • 5
  • Zodwa Dlamini
    • 1
  1. 1.College of Agriculture and Environmental ScienceUniversity of South AfricaJohannesburgSouth Africa
  2. 2.Biotechnology DepartmentUniversity of the Western CapeBellville, Cape TownSouth Africa
  3. 3.Mintek, National Innovation Centre (NIC) BiolabelsJohannesburgSouth Africa
  4. 4.School of Anatomical SciencesUniversity of the WitwatersrandParktownSouth Africa
  5. 5.Division of BiotechnologyAgricultural Research Council of South AfricaHatfield, PretoriaSouth Africa

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