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

Molecular Therapy Research Center, Sungkyunkwan University, Seoul 135-710, Korea.
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.
Mesh Terms:
Apoptosis, Cell Line, Tumor, Humans, Interferon Regulatory Factor-1, Neoplasms, Protein Processing, Post-Translational, Small Ubiquitin-Related Modifier Proteins, Thermodynamics, Transcription, Genetic
Proc. Natl. Acad. Sci. U.S.A. Oct. 23, 2007; 104(43);17028-33 [PUBMED:17942705]
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