Disease relevance of RBM17

• A similar role for SPF45 is demonstrated in the activation of a cryptic 3' ss generated by a mutation that causes human beta-thalassemia [1].
• Our analyses using tissue microarrays and sausages of tumors indicated that SPF45 is highly expressed in numerous carcinomas including bladder, breast, colon, lung, ovarian, pancreatic, and prostate [2].
• However, it is questionable as to whether the SPF 45 product provides protection against 45 minimal erythema doses [3].

High impact information on RBM17

• A detailed examination of the Drosophila Sex-lethal gene has led to two significant discoveries-the role of the splicing factor SPF45 in defining the site of exon ligation, and that alternative splicing can be regulated at the second step [4].
• Thus, SPF45-mediated drug resistance in A2780 cells may result in part from effects of SPF45 on the transcription or alternate splicing of ERbeta-regulated genes [5].
• A2780-SPF45 cells accumulated similar levels of doxorubicin as vector-transfected and parental A2780 cells, indicating that drug resistance is not due to differences in drug accumulation [5].
• The splicing factor SPF45 (RBM17) is frequently overexpressed in many solid tumors, and stable expression in HeLa cells confers resistance to doxorubicin and vincristine [5].
• We isolated the human homologue and examined the normal human tissue expression, tumor expression, and the phenotype caused by overexpression of human SPF45 [2].

Biological context of RBM17

• A novel DNA repair enzyme containing RNA recognition, G-patch and specific splicing factor 45-like motifs in the protozoan parasite Toxoplasma gondii [6].

Anatomical context of RBM17

• Simultaneously, other groups identified SPF45 as a component of the spliceosome that is involved in alternative splicing [2].
• Interestingly, this study revealed that overexpression of SPF45 in HeLa, a cervical carcinoma cell line, resulted in drug resistance to doxorubicin and vincristine, two chemotherapeutic drugs commonly used in cancer [2].

Associations of RBM17 with chemical compounds

• Our effort to identify novel drug-resistant genes in cyclophosphamide-resistant EMT6 mouse mammary tumors led us to the identification of SPF45 [2].

Other interactions of RBM17

• Coimmunoprecipitation experiments suggest that SPF45 and ERbeta physically interact in vivo [5].
• The parasite Toxoplasma gondii expresses a 55 kDa protein or TgDRE that belongs to a novel family of proteins characterized by the presence of three domains, a human splicing factor 45-like motif (SF), a glycine-rich motif (G-patch), and a RNA recognition motif (RRM) [7].

References