New post-translational protein modification of an important regulator of cellular sugar metabolism discovered – AG Schupp

Cells adapt their metabolism to the availability of nutrients. One of the most important sensors for glucose and fructose in liver and fat cells is the transcription factor ChREBP. After their uptake, glucose and fructose are converted by the cell and lead to an increased activity of ChREBP, which by means of an altered gene and protein expression leads to cellular adaptations to deal with the increased sugar exposure. A limited adaptation to elevated sugar exposure at the cellular level can lead to the development of glucose intolerance and insulin resistance.

The working group around Prof. Michael Schupp, together with partners from the Leibniz Institute for Molecular Pharmacology in Berlin Buch and the University of Oulu/Finland, has found a new chemical modification of the ChREBP protein. This new modification affects certain amino acid residues of ChREBP and is required for the full activity of the transcription factor. Pharmacological interventions to control this ChREBP modification could represent new therapeutic approaches for metabolic diseases.

Publication:
The glucose-sensing transcription factor ChREBP is targeted by proline hydroxylation
Steffi Heidenreich*, Pamela Weber*, Heike Stephanowitz, Konstantin M Petricek, Till Schütte, Moritz Oster, Antti M Salo, Miriam Knauer, Isabel Goehring, Na Yang, Nicole Witte, Anne Schumann, Manuela Sommerfeld, Matthias Muenzner, Johanna Myllyharju, Eberhard Krause, and Michael Schupp
*equally contributing first authors
J Biol Chem. 2020 Oct 6 Online ahead of print.
PMID: 33023907, DOI: 10.1074/jbc.RA120.014402

Contact