title: A novel member of the SAF (scaffold attachment factor)-box protein family inhibits gene expression and induces apoptosis.
abstract: The SLTM [SAF (scaffold attachment factor)-like transcription modulator] protein contains a SAF-box DNA-binding motif and an RNA-binding domain, and shares an overall identity of 34% with SAFB1 {scaffold attachment factor-B1; also known as SAF-B (scaffold attachment factor B), HET [heat-shock protein 27 ERE (oestrogen response element) and TATA-box-binding protein] or HAP (heterogeneous nuclear ribonucleoprotein A1-interacting protein)}. Here, we show that SLTM is localized to the cell nucleus, but excluded from nucleoli, and to a large extent it co-localizes with SAFB1. In the nucleus, SLTM has a punctate distribution and it does not co-localize with SR (serine/arginine) proteins. Overexpression of SAFB1 has been shown to exert a number of inhibitory effects, including suppression of oestrogen signalling. Although SLTM also suppressed the ability of oestrogen to activate a reporter gene in MCF-7 breast-cancer cells, inhibition of a constitutively active beta-galactosidase gene suggested that this was primarily the consequence of a generalized inhibitory effect on transcription. Measurement of RNA synthesis, which showed a particularly marked inhibition of [(3)H]uridine incorporation into mRNA, supported this conclusion. In addition, analysis of cell-cycle parameters, chromatin condensation and cytochrome c release showed that SLTM induced apoptosis in a range of cultured cell lines. Thus the inhibitory effects of SLTM on gene expression appear to result from generalized down-regulation of mRNA synthesis and initiation of apoptosis consequent upon overexpressing the protein. While indicating a crucial role for SLTM in cellular function, these results also emphasize the need for caution when interpreting phenotypic changes associated with manipulation of protein expression levels.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
authors.forename: Ching Wan
authors.initials: CW
authors.lastname: Chan
authors.forename: Youn-Bok
authors.initials: YB
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: Uney
authors.forename: Andrea
authors.initials: A
authors.lastname: Flynn
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Tobias
authors.forename: Michael
authors.initials: M
authors.lastname: Norman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D004965:Estrogen Antagonists / Q000737:chemistry; D004967:Estrogens / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D005810:Multigene Family / Q000235:genetics / Q000502:physiology*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; D004967:Estrogens; D036961:Matrix Attachment Region Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C523919:SLTM protein, mouse; C500609:scaffold attachment factor B1, mouse