A Novel Splicing Variant of Mouse Interleukin (IL)-24 Antagonizes IL-24-induced Apoptosis

• Published in: The Journal of biological chemistry Vol. 283; no. 43; pp. 28860 - 28872
• Main Authors: Sahoo, Anupama, Jung, Yun Min, Kwon, Ho-Keun, Yi, Hwa-Jung, Lee, Suho, Chang, Sunghoe, Park, Zee-Yong, Hwang, Ki-Chul, Im, Sin-Hyeog
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.10.2008; American Society for Biochemistry and Molecular Biology
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Apoptosis; Base Sequence; Chlorocebus aethiops; COS Cells; Cytokines - genetics; Cytokines - metabolism; Dimerization; Endoplasmic Reticulum - metabolism; HeLa Cells; Humans; Melanoma, Experimental; Mice; Models, Biological; Molecular Sequence Data; Sequence Homology, Amino Acid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M802510200

Alternative splicing of mRNA enables functionally diverse protein isoforms to be expressed from a single gene, allowing transcriptome diversification. Interleukin (IL)-24/MDA-7 is a member of the IL-10 gene family, and FISP (IL-4-induced secreted protein), its murine homologue, is selectively expressed and secreted by T helper 2 lymphocytes. A novel splice variant of mouse IL-24/FISP, designated FISP-sp, lacks 29 nucleotides from the 5′-end of exon 4 of FISP. The level of FISP-sp expression is 10% of the level of total primary FISP transcription. Unlike FISP, FISP-sp does not induce growth inhibition and apoptosis. FISP-sp is exclusively localized in endoplasmic reticulum, and its expression is up-regulated by endoplasmic reticulum stress. Our results suggest that the novel splicing variant FISP-sp dimerizes with FISP and blocks its secretion and inhibits FISP-induced apoptosis in vivo.