The Drosophila Retinoblastoma Binding Protein 6 Family Member Has Two Isoforms and Is Potentially Involved in Embryonic Patterning

International Journal of Molecular Sciences

Monde Ntwasa¹  Theresa H. T. Coetzer²  Brent Oosthuysen³  Ekene Nweke³  Ricardo Jorge Antunes³  Rodney Hull³  Umar-Faruq Cajee³  Lehlogonolo Mokgohloa³ 

[1] 3209 Scottsville, South Africa;School of Life Sciences, University of KwaZulu-Natal (Pietermaritzburg campus);School of Molecular & Cell Biology, University of the Witwatersrand, Johannesburg,South Africa Private Bag 3, WITS-2050 Johannesburg, South Africa;

关键词: retinoblastoma binding protein 6;    RBBP6;    SNAMA;    p53;    Rb;    Mdm2;   

DOI  :  10.3390/ijms160510242

来源: DOAJ

【 摘 要 】

The human retinoblastoma binding protein 6 (RBBP6) is implicated in esophageal, lung, hepatocellular and colon cancers. Furthermore, RBBP6 was identifiedas a strong marker for colon cancer prognosis and as a predisposing factor in familial myeloproliferative neoplasms. Functionally, the mammalian protein interacts with p53 and enhances the activity of Mdm2, the prototypical negative regulator of p53. However, since RBBP6 (known as PACT in mice) exists in multiple isoforms and pact−/− mice exhibit a more severe phenotype than mdm2−/− mutants, it must possess some Mdm2-independent functions. The function of the invertebrate homologue is poorly understood. This is complicated by the absence of the Mdm2 gene in both Drosophila and Caenorhabditis elegans. We have experimentally identified the promoter region of Snama, the Drosophila homologue, analyzed potential transcription factor binding sites and confirmed the existence ofan additional isoform. Using band shift and co-immunoprecipitation assays combined with mass spectrometry, we found evidence that this gene may be regulated by, amongst others, DREF, which regulates hundreds of genes related to cell proliferation. The potential transcription factors for Snama fall into distinct functional groups, including anteroposterior embryonic patterning and nucleic acid metabolism. Significantly, previous work in mice shows that pact−/− induces an anteroposterior phenotype in embryos when rescued by simultaneous deletion of p53. Taken together, these observations indicate the significance of RBBP6 proteins in carcinogenesis and in developmental defects.

【 授权许可】

Unknown