S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
DNA methyltransferase 3B mutant in ICF syndrome interacts non-covalently with SUMO-1
- Park, Jinah; Kim, Tae-You; Jung, Yeonjoo; Song, Sang-Hyun; Kim, Sung-Hak; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue
- Issue Date
- Springer Verlag
- J Mol Med. 2008 Nov;86(11):1269-77.
- Cell Line, Tumor; Cell Nucleus/metabolism; Centromere/genetics; *Chromosomal Instability; Craniofacial Abnormalities/*genetics; DNA (Cytosine-5-)-Methyltransferase/genetics/*metabolism; Face; Humans; Immunologic Deficiency Syndromes/*genetics; Interleukin-8/genetics; NF-kappa B/metabolism; Point Mutation; Promoter Regions, Genetic; Protein Binding; Protein Inhibitors of Activated STAT/metabolism; SUMO-1 Protein/*metabolism; Small Ubiquitin-Related Modifier Proteins/metabolism; Syndrome; Transcription Factors/metabolism; Transcription, Genetic
- Mutations of the DNA methyltransferase 3B (DNMT3B) gene have been detected in patients with immunodeficiency, centromere instability, and facial anomalies (ICF) syndrome. Most of these mutations are clustered in its catalytic domain and thus lead to defective DNA methylation. Nevertheless, the S270P mutation in the N-terminal PWWP (Pro-Trp-Trp-Pro) domain of the DNMT3B gene has prompted questions as to how this mutation contributes to the development of ICF syndrome. In this study, we found that wild-type DNMT3B is SUMOylated through covalent modification, whereas the S270P mutant interacts with SUMO-1 via non-covalent interaction. The S270P mutation results in diffuse nucleus localization. Moreover, the S270P mutant fails to interact with PIAS1, a small ubiquitin-related modifier (SUMO) E3 ligase, and causes the constitutive activation of nuclear factor-kappa B, which induces the expression of interleukin 8. Collectively, our data demonstrate that the S270P mutation affects DNMT3B functions via specific, non-covalent interaction with SUMO-1.
- 0946-2716 (Print)
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