title: Splice variants of mda-7/IL-24 differentially affect survival and induce apoptosis in U2OS cells.
abstract: Interleukin-24 (mda-7/IL-24) is a cytokine in the IL-10 family that has received a great deal of attention for its properties as a tumor suppressor and as a potential treatment for cancer. In this study, we have identified and characterized five alternatively spliced isoforms of this gene. Several, but not all of these isoforms induce apoptosis in the osteosarcoma cell line U2OS, while none affect the survival of the non-cancerous NOK cell line. One of these isoforms, lacking three exons and encoding the N-terminal end of the mda-7/IL-24 protein sequence, caused levels of apoptosis that were higher than those caused by the full-length mda-7/IL-24 variant. Additionally, we found that the ratio of isoform expression can be modified by the splice factor SRp55. This regulation suggests that alternative splicing of mda-7/IL-24 is under tight control in the cell, and can be modified under various cellular conditions, such as DNA damage. In addition to providing new insights into the function of an important tumor suppressor gene, these findings may also point toward new avenues for cancer treatment.
authors.affiliation: Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University, School of Medicine, Loma Linda, CA 92354, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Whitaker
authors.forename: Valery
authors.initials: V
authors.lastname: Filippov
authors.forename: Maria
authors.initials: M
authors.lastname: Filippova
authors.forename: Christian F
authors.initials: CF
authors.lastname: Guerrero-Juarez
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Duerksen-Hughes
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D006801:Humans; D007378:Interleukins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D012326:RNA Splicing; D017386:Sequence Homology, Amino Acid; D000099180:Interleukin-24
chemical_list: D017931:DNA Primers; D007378:Interleukins; D000099180:Interleukin-24