Combinatorial regulation by ERK1/2 and CK1δ protein kinases leads to HIF-1α association with microtubules and facilitates its symmetrical distribution during mitosis.

ABSTRACT: Hypoxia-inducible factor-1 (HIF-1) is the key transcriptional mediator of the cellular response to hypoxia and is also involved in cancer progression. Regulation of its oxygen-sensitive HIF-1α subunit involves post-translational modifications that control its stability, subcellular localization, and activity. We have previously reported that phosphorylation of the HIF-1α C-terminal domain by ERK1/2 promotes HIF-1α nuclear accumulation and stimulates HIF-1 activity while lack of this modification triggers HIF-1α nuclear export and its association with mitochondria. On the other hand, modification of the N-terminal domain of HIF-1α by CK1δ impairs HIF-1 activity by obstructing the formation of a HIF-1α/ARNT heterodimer. Investigation of these two antagonistic events by expressing double phos

SUBMITTER: Arseni C 

PROVIDER: S-EPMC10834586 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature