O-GlcNAcylation of the tumor suppressor LATS1 drives mitotic progression via PLK1.

ABSTRACT: Initially discovered in Drosophila, the Hippo pathway is pivotal for tissue growth and organ homeostasis. It is regulated by both extrinsic and intrinsic signals and exerts its effect via a core kinase cascade, in which large tumor suppressor 1 and 2 (LATS1/2) plays a key role. LATS1 has also been shown to regulate mitotic progression by phosphorylating myosin phosphatase targeting subunit 1 (MYPT1) to counteract the activity of polo-like kinase 1 (PLK1), a mitotic master kinase. Herein, we demonstrate that the hexosamine biosynthetic pathway regulates the Hippo pathway via LATS1. We show that LATS1 interacts with the O-GlcNAc transferase (OGT) and is O-GlcNAcylated. Via electron transfer dissociation mass spectrometry, we mapped the O-GlcNAcylation sites to be S479/S482/T484/T485. O-GlcNA

SUBMITTER: Meng L 

PROVIDER: S-EPMC12797046 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature