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

Junsoo Park, Kwangsoo Kim, Eun Ju Lee, Yun Jee Seo, Si Nae Lim, Kyoungsook Park, Bae Rho Seung, Seung Hoon Lee, Je Ho Lee

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)17028-17033
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number43
DOIs
Publication statusPublished - 2007 Oct 23

All Science Journal Classification (ASJC) codes

  • General

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