DNA methylation modifier LSH inhibits p53 ubiquitination and transactivates p53 to promote lipid metabolism

Release time:2020-07-12

Impact Factor:4.237

Affiliation of Author(s):中南大学

Teaching and Research Group:病理学系

Journal:Epigenetics Chromatin

Key Words:DUB; LSH; Lipid metabolism; P53; PKM2

Abstract:Background: The stability of p53 is mainly controlled by ubiquitin-dependent degradation, which is triggered by the E3 ubiquitin ligase MDM2. The chromatin modifier lymphoid-specific helicase (LSH) is essential for DNA methylation and cancer progression as a transcriptional repressor. The potential interplay between chromatin modifiers and transcription factors remains largely unknown. Results: Here, we present data suggesting that LSH regulates p53 in cis through two pathways: prevention proteasomal degradation through its deubiquitination, which is achieved by reducing the lysine 11-linked, lysine 48-linked polyubiquitin chains (K11 and K48) on p53; and revival of the transcriptional activity of p53 by forming a complex with PKM2 (pyruvate kinase 2). Furthermore, we confirmed that the LSH-PKM2 interaction occurred at the intersubunit interface region of the PKM2 C-terminal region and the coiled-coil domains (CC) and ATP-binding domains of LSH, and this interaction regulated p53-mediated transactivation in cis in lipid metabolism, especially lipid catabolism. Conclusion: These findings suggest that LSH is a novel regulator of p53 through the proteasomal pathway, thereby providing an alternative mechanism of p53 involvement in lipid metabolism in cancer.

Co-author:Ying Shi, Na Liu, Zuli Wang, Rui Yang, Bin Yan, Xiaoli Liu, Weiwei Lai,Yating Liu, Desheng Xiao, Hu Zhou, Yan Cheng, Ya Cao, Shuang Liu

First Author:Ling Chen

Indexed by:Journal paper

Correspondence Author:Zanxian Xia, Yongguang Tao

Issue:12(1)

Page Number:59

Translation or Not:no

Date of Publication:2019-10-08

Included Journals:SCI