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

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 confirme

SUBMITTER: Chen L 

PROVIDER: S-EPMC6781351 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature