A novel member of the SAF (scaffold attachment factor)-box protein family inhibits gene expression and induces apoptosis
Résumé
The SLTM protein contains a SAF Box DNA binding motif, an RNA binding domain, and shares an overall identity of 34% with SAFB1 (also known as SAF-B, HET or HAP). Here, we show that SLTM is localised to the cell nucleus but excluded from nucleoli, and to a large extent it co-localises with SAFB1. In the nucleus, SLTM has a punctate distribution that does not co-localise with serine/arginine (SR) proteins. Over expression 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 β-galactosidase gene suggested that this was primarily the consequence of a generalised 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 inhibitory effects of SLTM on gene expression appear to result from generalised down-regulation of mRNA synthesis and initiation of apoptosis consequent upon over expressing the protein. While indicating a crucial role for SLTM in cellular function, these results also emphasise the need for caution when interpreting phenotypic changes associated with manipulation of protein expression levels
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