SAFB1- and SAFB2-mediated transcriptional repression: relevance to cancer.

SAFB1 (scaffold attachment factor B1) and a second family member SAFB2, are multifunctional proteins implicated in a variety of cellular processes including cell growth, apoptosis and stress response. Their potential function as tumour suppressors has been proposed based on well-described roles in tran-scriptional repression. The present review summarizes the current knowledge of SAFB1 and SAFB2 proteins in transcriptional repression with relevance to cancer.

Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells.

Up-regulation of the apoptosis-regulatory gene Mcl-1 (myeloid cell leukemia-1) occurs in different cancer types and is linked with drug resistance to cancer therapies. It is well known that Mcl-1 pre-mRNA undergoes alternative splicing events to produce two functionally distinct proteins, Mcl-1(S) (pro-apoptotic) and Mcl-l(L) (anti-apoptotic); the latter isoform is predominant in different cancers including breast and ovarian cancer cells. In the present study we report that the RNA-binding protein (RBP) and proto-oncogene SRSF1 (serine and arginine-rich splicing factor 1) influences splicing of Mcl-1 in both MCF-7 and MDA-MB-231 breast cancer cells and JAR choriocarcinoma cells; we also show for the first time that another RBP SRSF5 affects splicing of Mcl-1 in the MCF-7 cells. Moreover, we report that SRSF1 is involved in other aspects of Mcl-1 regulation with knockdown of SRSF1, by RNAi, resulting in a significant decrease in Mcl-1 protein levels in MCF-7 cells but an increase in JAR cells, respectively, by potentially affecting protein stability and translation of Mcl-l. The key findings from this study highlight the importance of the cellular context of different cancer cells for the function of multifunctional RBPs like SRSF1 and have implications for therapeutic approaches employed to target Mcl-1.