Colloquium Molecular Cell Biology

30.07.2025

The Transcription Factor Hif1α Moonlights as a Translation Modulator

Speaker:
Prof. Dr. Gunnar Dittmar (Luxembourg Institute of Health, Department of Infection and Immunity)

Host:
Konstanze F. Winklhofer
Institute of Biochemistry and Pathobiochemistry, Molecular Cell Biology (RUB)

Venue:
MA 2/139

Starting time:
4:00 pm

Abstract:
The transcription factor HIF1 is the master regulator for the metabolic switch from oxidative phosphorylation to glycolysis under hypoxia. This switch is crucial during myocardial infarction, stroke or in the core of solid tumors, where cells are deprived of oxygen. HIF1 comprises two subunits, HIF1α and HIF1β, which are continuously expressed. While HIF1β remains stable, HIF1α is rapidly degraded under normoxic conditions by the VHL-E3 ligase complex and the proteasome. However, when oxygen levels drop, HIF1α is stabilized and pairs with HIF1β to form the active HIF1 transcription factor.

The role of Hif1α is well-studied, although new research indicates additional functions. To identify new interaction partners for HIF1α, we utilized PrISMa, a technology that allows the rapid identification of protein-protein interactions and their interaction sites by mass spectrometry. We identified the EIF3 translation complex as the highest-scoring interactor and confirmed this result in cells by independent methods, studying the endogenous HIF1α as well as genetic mutants. We validated the presence of HIF1α in polysomes in active sites of translation, and mass spectrometry-based measurements of the translation rate indicate that HIF1α regulates the translation of a subset of genes.