Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell lines

• Published in: Animal cells and systems Vol. 22; no. 1; pp. 22 - 28
• Main Authors: Yu, Seung Eun, Park, Su Hyung, Jang, Yeun Kyu
• Format: Journal Article
• Language: English
• Published: Daejeon Taylor & Francis 02.01.2018; Taylor & Francis Ltd; Taylor & Francis Group; 한국통합생물학회
• Subjects: Binding; Cancer; Cell cycle; Chromatin; Colon; Colon cancer; Colon cancer cells; Gene expression; Gene regulation; histone demethylase; Immunoprecipitation; KDM4A; Localization; Lysine; Mutants; p53; p53 Protein; Post-translation; SUMO protein; sumoylation; Tumor cell lines; Tumor suppressor genes; Ubiquitin; 생물학
• ISSN: 1976-8354; 2151-2485
• DOI: 10.1080/19768354.2018.1426628

The histone demethylase lysine-specific demethylase 4A (KDM4A/Jmjd2A) has diverse functions, including involvement in gene regulation and cell cycle, and plays an oncogenic role in cancer cells. The modulation of KDM4A through post-translational modifications remains unclear. Here, we show that small ubiquitin-like modifier (SUMO) 1-mediated modification of KDM4A was required for interaction with tumor suppressor p53. Our data revealed that KDM4A is mainly sumoylated at lysine residue 471. However, the SUMO modification resulted in little change in subcellular localization, demethylase activity, or protein stability of KMD4A. Intriguingly, co-immunoprecipitation data revealed that sumoylation-defective mutants of KDM4A had a lower binding ability with p53 compared to that of wild-type KDM4A, suggesting a positive role for sumoylation in the interaction between KDM4A and p53. Together, these data suggest that KDM4A is post-translationally modified by SUMO, and this sumoylation may be a novel regulatory switch for controlling the interplay between KDM4A and p53.