title: Candidate tumour suppressor Fau regulates apoptosis in human cells: an essential role for Bcl-G.
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.
authors.affiliation: Institute of Science and Technology in Medicine, Huxley Building, Keele University, Keele, ST5 5BG, UK. m.r.pickard@biol.keele.ac.uk
authors.forename: Mark R
authors.initials: MR
authors.lastname: Pickard
authors.forename: Mirna
authors.initials: M
authors.lastname: Mourtada-Maarabouni
authors.forename: Gwyn T
authors.initials: GT
authors.lastname: Williams
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D012269:Ribosomal Proteins / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D014466:Ultraviolet Rays
chemical_list: C428448:BCL2L14 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012269:Ribosomal Proteins; D025521:Tumor Suppressor Proteins; C076845:FAU protein, human