title: The p36 isoform of BAG-1 is translated by internal ribosome entry following heat shock.
abstract: BAG-1 (also known as RAP46/HAP46) was originally identified as a 46 kDa protein that bound to and enhanced the anti-apoptotic properties of Bcl-2. BAG-1 exists as three major isoforms (designated p50, p46 and p36 or BAG-1L, BAG-1M and BAG-1S respectively) and one minor isoform (p29), which are translated from a common transcript. The differing amino terminus determines both the intracellular location and the repertoire of binding partners of the isoforms which play different roles in a variety of cellular processes including signal transduction, heat shock, apoptosis and transcription. Although in vitro data suggest that the four BAG-1 isoforms are translated by leaky scanning, the patterns of isoform expression in vivo, especially in transformed cells, do not support this hypothesis. We have performed in vivo analysis of the BAG-1 5' untranslated region and shown that translation initiation of the most highly expressed isoform (p36/BAG-1S) can occur by both internal ribosome entry and cap-dependent scanning. Following heat shock, when there is a downregulation of cap-dependent translation, the expression of the p36 isoform of BAG-1 is maintained by internal ribosome entry.
authors.affiliation: Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Coldwell
authors.forename: M L
authors.initials: ML
authors.lastname: deSchoolmeester
authors.forename: G A
authors.initials: GA
authors.lastname: Fraser
authors.forename: B M
authors.initials: BM
authors.lastname: Pickering
authors.forename: G
authors.initials: G
authors.lastname: Packham
authors.forename: A E
authors.initials: AE
authors.lastname: Willis
mesh_terms: D020121:5' Untranslated Regions; D017209:Apoptosis; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins; D017930:Genes, Reporter; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D012315:RNA Caps / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012270:Ribosomes / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D020121:5' Untranslated Regions; C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012315:RNA Caps; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D008156:Luciferases