Their data do not selleckchem directly support our present hypothesis, which is similar to their hypothesis that if one function of the WRN heli case were to resolve non B struc tures, as observed in vitro, then mutation frequencies may be higher in WRN deficient cells than in WRN wild type cells because both the number and stability of such structures would be greater in WRN deficient cells. However, they did verify that purified WRN protein was able to unwind the third purine rich strand of a synthetic triplex in vitro. Although our data suggest a correlation between expression of the WRN helicase with triplex DNA binding activity in both normal and tumor tissue extracts, defining a functional role and mechanism of non B DNA unwinding Inhibitors,Modulators,Libraries activity by WRN helicase and G G multiplex binding will re quire further study.

Beta catenin, as a transcription factor complexed with TCF4, is known to upregulate expression of many rele vant proteins in colorectal cancer, such as c myc, cyclin D1, LEF 1, CD44, and c jun. Whether beta catenin influences the expression of U2AF65 is unknown, but a search of transcription factor binding sites in the U2AF65 gene promoter did Inhibitors,Modulators,Libraries not indicate any beta catenin or TCF family transcription factor sites among the 55 high scoring sites we identified as a beta catenin, TCF4, or Wnt target gene The biological significance of the correlation of U2AF65 and beta catenin expression Inhibitors,Modulators,Libraries in colorectal tumor tissues, such as if beta catenin as a transcription factor affects U2AF65 expression, or if U2AF65 as a splicing factor affects the splicing Inhibitors,Modulators,Libraries or expres sion of beta catenin, remains to be determined.

Several studies have Inhibitors,Modulators,Libraries examined the interaction of beta catenin with Alvespimycin splicing factors and the role of beta catenin in mRNA splicing. Researchers identified alternative spli cing of SLC39A14, a divalent cation transporter, in colo rectal tumors and found it to be regulated by the Wnt pathway, probably through regulation of splicing factor SRSF1. The beta catenin TCF4 pathway also modifies alternative splicing through modulation of expression of splicing factors SRp20 and SF1 and direct inter action with FUS TLS and various other RNA binding proteins, including p54nrb. Others have shown that beta catenin regulates mul tiple steps of RNA metabolism in colon cancer cells and may coordinate RNA metabolism. Authors have also reported identification of truncated beta catenin isoforms, mostly in colorectal cancer cells. In primary colorectal tumors, a relatively small percent contained somatic interstitial deletions that included all or part of exon 3 of the beta catenin gene, and RT PCR analysis from 3 of the 7 tumors detected tran scripts that lacked exon 3 and the presence of the normal transcript.