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

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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.

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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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Authors and Affiliations

  1. College of Agriculture and Environmental Science, University of South Africa, Florida Campus, Corner Christian de Vet Ave and Pioneer, Johannesburg, 1710, South Africa

    Zukile Mbita & Zodwa Dlamini

  2. Biotechnology Department, University of the Western Cape, Bellville, Cape Town, 7535, South Africa

    Mervin Meyer

  3. Mintek, National Innovation Centre (NIC) Biolabels, Johannesburg, 2125, South Africa

    Amanda Skepu

  4. School of Anatomical Sciences, University of the Witwatersrand, Parktown, 2193, South Africa

    Margot Hosie

  5. Division of Biotechnology, Agricultural Research Council of South Africa, Hatfield, Pretoria, 0001, South Africa

    Jasper Rees

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  1. Zukile Mbita
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  2. Mervin Meyer
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  3. Amanda Skepu
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  4. Margot Hosie
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  5. Jasper Rees
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  6. Zodwa Dlamini
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Correspondence to Zodwa Dlamini.

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Mbita, Z., Meyer, M., Skepu, A. et al. De-regulation of the RBBP6 isoform 3/DWNN in human cancers. Mol Cell Biochem 362, 249–262 (2012). https://doi.org/10.1007/s11010-011-1150-5

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  • DOI: https://doi.org/10.1007/s11010-011-1150-5

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