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J Biol Chem, Vol. 274, Issue 35, 24766-24772, August 27, 1999

A Novel Oncostatin M-inducible Gene OIG37 Forms a Gene Family with MyD118 and GADD45 and Negatively Regulates Cell Growth

Koh Nakayama, Takahiko Hara, Masahiko Hibi^§, Toshio Hirano^§, and Atsushi Miyajima

From the  Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan and the ^§ Osaka University School of Medicine, Suita-shi 565-0871, Japan

Oncostatin M (OSM) is a member of the IL-6 family cytokines that use gp130 as a common signal transducer and exhibits both growth stimulatory as well as growth inhibitory activity depending on the cells. To analyze the mechanism of OSM function, we isolated immediate early responsive genes upon OSM stimulation. Here we describe the novel OSM-inducible gene OIG37 that is related to MyD118 and GADD45. The MyD118 gene has been described as an immediate early gene induced by IL-6 in M1 monocytic cells, and GADD45 was identified as a gene induced by UV or -ray irradiation. Both are considered to function in growth arrest and/or DNA repair. Although the expression of OIG37, MyD118, and GADD45 was rather ubiquitous, it was differentially regulated. As the gp130 mutant defective for activating the STAT3 pathway showed the reduced induction of OIG37 by cytokine stimulation and expression of dominant negative STAT3 inhibited the induction of OIG37 by OSM, STAT3 is involved in OIG37 induction by IL-6 family cytokines. To examine the function of OIG37, we expressed it in NIH3T3 and IL-3-dependent BaF3 cells and found that OIG37 suppressed cell growth without any evidence of apoptosis. Whereas both MyD118 and OIG37 suppressed cell growth in both cell lines, suppression by OIG37 was more efficient than by MyD118. Immunoprecipitation experiments indicated that OIG37 associates with p21, a cyclin-dependent kinase inhibitor, and proliferating cell nuclear antigen.

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