Phosphorylation determines the glucose metabolism reprogramming and tumor-promoting activity of sine oculis homeobox 1.

ABSTRACT: Aerobic glycolysis is a hallmark of cancer and is regulated by growth factors, protein kinases and transcription factors. However, it remains poorly understood how these components interact to regulate aerobic glycolysis coordinately. Here, we show that sine oculis homeobox 1 (SIX1) phosphorylation integrates growth factors (e.g. TGFβ, EGF) to control aerobic glycolysis and determines its tumor-promoting activity. SIX1 is phosphorylated at serine 225 (S225) by growth factors-activated protein kinases ERK1/2 and its phosphorylation is responsible for glycolysis stimulated by some growth factors. SIX1 is dephosphorylated by the atypical protein phosphatase eyes absent 4 (EYA4). Phosphorylation blocks non-canonical ubiquitination and degradation of SIX1 through the E3 ubiquitin ligase FZR1. U

SUBMITTER: Lin Y 

PROVIDER: S-EPMC11609306 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature