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DNA Methylation Modifier LSH Inhibits p53 Ubiquitination and Transactivates p53 to Promote Lipid Metabolism

DNA Methylation Modifier LSH Inhibits p53 Ubiquitination and Transactivates p53 to Promote Lipid Metabolism

Ling Chen, 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, Zanxian Xia, Yongguang Tao

Epigenetics Chromatin. 2019 Oct 8;12(1):59.

PMID: 31594538

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP133407826-B	MG-132 - CAS 133407-82-6		133407-82-6	Price

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