Candidate tumour suppressor Fau regulates apoptosis in human cells: An essential role for Bcl-G

Pickard, Mark R.; Mourtada-Maarabouni, Mirna; Williams, Gwyn T.

Abstract

FAU, which encodes a ubiquitin-like protein (termed FUBI) with ribosomal protein S30 as a carboxy-terminal extension, has recently been identified as a pro-apoptotic regulatory gene. This activity may be mediated by Bcl-G (a pro-apoptotic member of the Bcl-2 family) which can be covalently modified by FUBI. FAU gene expression has been shown to be down-regulated in human breast, prostate and ovarian tumours, and this down-regulation is strongly associated with poor prognosis in breast cancer. We demonstrate here that ectopic FAU expression increases basal apoptosis in human T-cell lines and 293T/17 cells, whereas it has only a transient stimulatory effect on ultraviolet-C (UVC)-induced apoptosis. Conversely, siRNA-mediated silencing of FAU gene expression has no effect on basal apoptosis, but attenuates UV-induced apoptosis. Importantly, prior knockdown of Bcl-G expression ablates the stimulation of basal apoptosis by FAU, consistent with an essential downstream role for Bcl-G, itself a candidate tumour suppressor, in mediating the apoptosis regulatory role of FAU. In 293T/17 cells, Bcl-G knockdown also attenuates UV-induced apoptosis, so that Bcl-G may constitute a common factor in the pathways by which both FAU and UV-irradiation induce apoptosis. UV irradiation increases Bcl-G mRNA levels, providing an explanation for the transient nature of the effect of ectopic FAU expression on UV-induced apoptosis. Since failure of apoptosis is fundamental to the development of many cancers, the pro-apoptotic activity of the Fau/Bcl-G pathway offers an attractive explanation for the putative tumour suppressor role of FAU.

Citation

Pickard, M. R., Mourtada-Maarabouni, M., & Williams, G. T. (2011). Candidate tumour suppressor Fau regulates apoptosis in human cells: An essential role for Bcl-G. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1812(9), 1146-1153. https://doi.org/10.1016/j.bbadis.2011.04.009

• Journal Article Type: Article
• Acceptance Date: Apr 21, 2011
• Online Publication Date: Apr 29, 2011
• Publication Date: 2011-09
• Deposit Date: May 16, 2024
• Journal: Biochimica et Biophysica Acta - Molecular Basis of Disease
• Print ISSN: 0925-4439
• Electronic ISSN: 1879-260X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 1812
• Issue: 9
• Pages: 1146-1153
• ISBN: 09254439 1879260X
• DOI: https://doi.org/10.1016/j.bbadis.2011.04.009
• Public URL: https://keele-repository.worktribe.com/output/543699
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0925443911000925?via%3Dihub