The biochemical functions of the Retinoblastoma binding protein 6 (RBBP 6) isoforms in metabolic reprogramming occurring during carcinogenesis

• Main Author: Nsingwane, Zanele
• Format: Others
• Language: en
• Published: 2018
• Subjects: Carcinogenesis; Protein binding; Cancer cells
• Online Access: Nsingwane, Zanele (2018) The biochemical functions of the Retinoblastoma binding protein 6 (RBBP 6) isoforms in metabolic reprogramming occurring during carcinogenesis, University of the Witwatersrand, Johannesburg, <http://hdl.handle.net/10539/25653>; https://hdl.handle.net/10539/25653

Thesis (M.Sc.)--University of the Witwatersrand, Faculty of Science, School of Molecular and Cell Biology, 2018. === ABSTRACT The Retinoblastoma binding protein 6 is dysregulated in most cancers, indicating it may play a role in metabolic reprograming- a hallmark of carcinogenesis. Its human isoforms have been shown to play diverse roles in apoptosis. This study aimed to elucidate biochemical roles of RBBP6 isoforms in metabolic reprogramming during carcinogenesis. Drosophila melanogaster wild type and p53 null mutants were treated with drug permutations of irinotecan (DNA damaging agent) and exogenous pyruvate to perturb metabolism. Moreover, using RT-PCR and Western blot expression profiles of SNAMA (Drosophila Orthologue of RBBP6) isoforms were shown followed by survival studies to investigate the effects of these drugs. Furthermore, using bioinformatics the domains of RBBP6 isoforms in various species were shown. Results indicate that RBBP6 isoforms show contrasting expression patterns. Furthermore, exogenous pyruvate protects the wild type flies from irinotecan toxicity while killing p53 null mutants. RBBP6 proves to be a potential druggable target for chemotherapy. === EM2018