title: Regulation of apoptosis by fau revealed by functional expression cloning and antisense expression.
abstract: Functional expression cloning is a powerful strategy for identifying critical steps in biological pathways independently of prior assumptions. It is particularly suitable for the identification of molecules crucial to the control of apoptosis. Our screen for sequences suppressing T-cell apoptosis isolated a sequence antisense to fau (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene). The fox gene in FBR murine osteosarcoma virus is also antisense to fau and several reports have indicated that fau displays tumour suppressor and oncogenic properties in different contexts. Our observations indicate that the fau antisense sequence suppresses expression of endogenous fau mRNA and produces resistance to apoptosis induced both by the glucocorticoid analogue dexamethasone' by ultraviolet radiation, and by the anticancer drug cisplatin. In all cases, colony-forming ability is protected, indicating that fau affects the critical events prior to commitment to cell death. Overexpression of fau in the sense orientation induces cell death, which is inhibited both by Bcl-2 and by inhibition of caspases, in line with its proposed role in apoptosis.
authors.affiliation: School of Life Sciences, Keele University, Keele, ST5 5BG, UK. bia19@biol.keele.ac.uk
authors.forename: Mirna
authors.initials: M
authors.lastname: Mourtada-Maarabouni
authors.forename: Lucy
authors.initials: L
authors.lastname: Kirkham
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
authors.forename: Gwyn T
authors.initials: GT
authors.lastname: Williams
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D008969:Molecular Sequence Data; D012269:Ribosomal Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D012269:Ribosomal Proteins; C076845:FAU protein, human; D004247:DNA