Journal of Molecular Medicine

, Volume 86, Issue 11, pp 1269–1277 | Cite as

DNA methyltransferase 3B mutant in ICF syndrome interacts non-covalently with SUMO-1

  • Jinah Park
  • Tae-You Kim
  • Yeonjoo Jung
  • Sang-Hyun Song
  • Sung-Hak Kim
  • Do-Youn Oh
  • Seock-Ah Im
  • Yung-Jue BangEmail author
Original Article


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.


DNMT3B ICF syndrome SUMOylation S270P mutation 



We thank Dr. Jong-Soo Lee (Ajou University, Korea) for discussions and providing the SUMO-1 constructs. We also thank all members of Bang’s laboratory. This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the National Research Lab. Program funded by the Ministry of Science and Technology (No.M10400000336-06J0000-33610) and the BK21 Project for Medicine, Dentistry and Pharmacy.

Supplementary material

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ESM 1 (DOC 954 KB)


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Jinah Park
    • 1
  • Tae-You Kim
    • 1
    • 2
  • Yeonjoo Jung
    • 1
  • Sang-Hyun Song
    • 3
  • Sung-Hak Kim
    • 1
  • Do-Youn Oh
    • 1
    • 2
  • Seock-Ah Im
    • 1
    • 2
  • Yung-Jue Bang
    • 1
    • 2
    Email author
  1. 1.National Research Laboratory for Cancer EpigeneticsCancer Research InstituteSeoulKorea
  2. 2.Department of Internal MedicineSeoul National University College of MedicineSeoulKorea
  3. 3.The Laboratory of Cellular and Development Biology, NIDDKNational Institutes of HealthBethesdaUSA

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