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

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 smal...

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Main Authors: Seung Eun Yu, Su Hyung Park, Yeun Kyu Jang
Format: Article
Language:English
Published: Taylor & Francis Group 2018-01-01
Series:Animal Cells and Systems
Subjects:
Online Access:http://dx.doi.org/10.1080/19768354.2018.1426628
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author Seung Eun Yu
Su Hyung Park
Yeun Kyu Jang
author_facet Seung Eun Yu
Su Hyung Park
Yeun Kyu Jang
author_sort Seung Eun Yu
collection DOAJ
description 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.
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spelling doaj.art-853e3a8faf9a41b3a08db291fa3fe7772022-12-21T18:24:15ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852018-01-01221222810.1080/19768354.2018.14266281426628Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell linesSeung Eun Yu0Su Hyung Park1Yeun Kyu Jang2Yonsei UniversityYonsei UniversityYonsei UniversityThe 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.http://dx.doi.org/10.1080/19768354.2018.1426628Colon cancer cellshistone demethylaseKDM4Ap53sumoylation
spellingShingle Seung Eun Yu
Su Hyung Park
Yeun Kyu Jang
Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell lines
Animal Cells and Systems
Colon cancer cells
histone demethylase
KDM4A
p53
sumoylation
title Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell lines
title_full Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell lines
title_fullStr Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell lines
title_full_unstemmed Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell lines
title_short Sumoylation of the histone demethylase KDM4A is required for binding to tumor suppressor p53 in HCT116 colon cancer cell lines
title_sort sumoylation of the histone demethylase kdm4a is required for binding to tumor suppressor p53 in hct116 colon cancer cell lines
topic Colon cancer cells
histone demethylase
KDM4A
p53
sumoylation
url http://dx.doi.org/10.1080/19768354.2018.1426628
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AT yeunkyujang sumoylationofthehistonedemethylasekdm4aisrequiredforbindingtotumorsuppressorp53inhct116coloncancercelllines