title: Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis.
abstract: 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-alpha/beta, 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.
authors.affiliation: Molecular Therapy Research Center, Sungkyunkwan University, Seoul 135-710, Korea.
authors.forename: Junsoo
authors.initials: J
authors.lastname: Park
authors.forename: Kwangsoo
authors.initials: K
authors.lastname: Kim
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Yun-Jee
authors.initials: YJ
authors.lastname: Seo
authors.forename: Si-Nae
authors.initials: SN
authors.lastname: Lim
authors.forename: Kyoungsook
authors.initials: K
authors.lastname: Park
authors.forename: Seung Bae
authors.initials: SB
authors.lastname: Rho
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Je-Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013816:Thermodynamics; D014158:Transcription, Genetic
chemical_list: D050856:Interferon Regulatory Factor-1; D025841:Small Ubiquitin-Related Modifier Proteins