Nucleus-translocated glucokinase functions as a protein kinase to phosphorylate TAZ and promote tumour growth.

ABSTRACT: Hypoxia frequently occurs during rapid tumour growth. However, how tumour cells adapt to hypoxic stress by remodeling central cellular pathways remains largely unclear. Here, we show that hypoxia induces casein kinase 2 (CK2)-mediated glucokinase (GCK) S398 phosphorylation, which exposes its nuclear localization signal (NLS) for importin α1 binding and nuclear translocation. Importantly, nuclear GCK interacts with the transcriptional coactivator with PDZ-binding motif (TAZ) and functions as a protein kinase that phosphorylates TAZ T346. Phosphorylated TAZ recruits peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) for cis-trans isomerization of TAZ, which inhibits the binding of β-TrCP to TAZ and β-TrCP-mediated TAZ degradation. Activated TAZ-TEAD induces the expression of downs

SUBMITTER: Zhao G 

PROVIDER: S-EPMC12322040 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature