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Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis

Park, Junsoo, Kim, Kwangsoo, Lee, Eun-Ju, Seo, Yun-Jee, Lim, Si-Nae, Park, Kyoungsook, Rho, Seung Bae, Lee, Seung-Hoon, Lee, Je-Ho
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.43 pp. 17028-17033
apoptosis, gene expression, immune response, interferon regulatory factor-1, neoplasm cells, neoplasms, phenotype, site-directed mutagenesis, transcription (genetics), ubiquitination
SUMOylation of transcription factors often attenuates transcription activity. This regulation of protein activity allows more diversity in the control of gene expression. Interferon regulatory factor-1 (IRF-1) was originally identified as a regulator of IFN-α/β, and its expression is induced by viral infection or IFN stimulation. Accumulating evidence supports the theory that IRF-1 functions as a tumor suppressor and represses the transformed phenotype. Here we report that the level of SUMOylated IRF-1 is elevated in tumors. Site-directed mutagenesis experiments disclose that the SUMOylation sites of IRF-1 are identical to the major ubiquitination sites. Consequently, SUMOylated IRF-1 displays enhanced resistance to degradation. SUMOylation of IRF-1 attenuates its transcription activity, and SUMOylated IRF-1 inhibits apoptosis by repression of its transcriptional activity. These data support a mechanism whereby SUMOylation of IRF-1 inactivates its tumor suppressor function, which facilitates resistance to the immune response.