Splice variants in apoptotic pathway.
Elimination of superfluous or mutated somatic cells is provided by various mechanisms including apoptosis, and deregulation of apoptotic signaling pathways contributes to oncogenesis. 40 years have passed since the term "apoptosis" was introduced by Kerr et al. in 1972; among the programmed cell death, a variety of therapeutic strategies especially targeting apoptotic pathways have been investigated. Alternative precursor messenger RNA splicing, by which the process the exons of pre-mRNA are spliced in different arrangements to produce structurally and functionally distinct mRNA and proteins, is another field in progress, and it has been recognized as one of the most important mechanisms that maintains genomic and functional diversity. A variety of apoptotic genes are regulated through alternative pre-mRNA splicing as well, some of which have important functions as pro-apoptotic and anti-apoptotic factors. In this article we summarized splice variants of some of the apoptotic genes including BCL2L1, BIRC5, CFLAR, and MADD, as well as the regulatory mechanisms of alternative splicing of these genes. If the information of the apoptosis and aberrant splicing in each of malignancies is integrated, it will become possible to target proper variants for apoptosis, and the trans-elements themselves can become specific targets of cancer therapy as well. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Japan. k-miura@surg1.med.tohoku.ac.jp
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Fujibuchi
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D017398:Alternative Splicing / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000077022:Survivin; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; D051034:Inhibitor of Apoptosis Proteins; C105852:MADD protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D000077022:Survivin; D051020:bcl-X Protein