Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis.
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.
Park
Junsoo
J
Molecular Therapy Research Center, Sungkyunkwan University, Seoul 135-710, Korea.
Kim
Kwangsoo
K
Lee
Eun-Ju
EJ
Seo
Yun-Jee
YJ
Lim
Si-Nae
SN
Park
Kyoungsook
K
Rho
Seung Bae
SB
Lee
Seung-Hoon
SH
Lee
Je-Ho
JH
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
D050856:Interferon Regulatory Factor-1; D025841:Small Ubiquitin-Related Modifier Proteins