Dr Cécile POLGE

Research interests

Inhibition of muscle atrophy during catabolic states

Contractile proteins represent a major AA reservoir of the organism. Proteolysis plays a key role in controlling muscle growth and atrophy and Ubiquitin Proteasome System (UPS) is responsible for the degradation of the major contractile proteins. This process requires 2 classes of enzymes that, through their interaction, confer targeting selectivity: the E2s (≈40 members) generally bring the catalytic activity and the E3s (> 700 members) recognize the substrate, an E2 being able to interact with several E3s and vice versa.

There is currently no treatment to limit muscle wasting that occurs during catabolic states. Our goal is to better understand the degradation of contractile proteins by the UPS to open new avenues for fighting against muscle atrophy: 

1) We aim to identify among the 14 poorly characterized muscular E2s, those involved in muscle atrophy. We already identified the E2 enzymes functionally interacting with MuRF1, the only E3 known to target contractile proteins.

2) Since MuRF1 is the major actor of contractile protein degradation, we are currently looking for MuRF1 pharmacological inhibitors.

We routinely use in vitro approaches and a variety of cellular and animal (rodents) catabolic models. We are also specialised in studying protein-protein interactions using complementary approaches such as the yeast two- and three-hybrid systems, surface plasmon resonance (SPR ; Biacore) and the modification of fluorescence properties induced by the binding of a partner (MonolithX)

5 main publications

• Claustre A, Malige M, Macheton M, Combaret L, Lefai E, Fafournoux P, Taillandier D, Henri J, Polge, C. (2025) Structure predictions of MuRF1-UBE2 complexes identified residues governing interaction selectivity for each MuRF1-E2 pair. FEBS J. 2025 Feb 10. doi: 10.1111/febs.70017.
• Polge, C; Cabantous, S and Taillandier, D. (2024) Tripartite split-GFP for high throughput screening of small molecules: a powerful strategy for targeting transient/labile interactors like E2-E3 ubiquitination enzymes. Chem.Bio.Chem 25(6). https://dx.doi.org/10.1002/cbic.202300723
• Peris-Moreno D., Malige M., Claustre A., Armani A., Coudy-Gandilhon C., Deval C., Béchet D., Fafournoux P., Sandri M., Combaret L., Taillandier D., Polge C. (2021). UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin. Cells, 10 (8), 1974, https://dx.doi.org/10.3390/cells10081974 .
• Peris-Moreno D., Taillandier D., Polge C. (2020). MuRF1/TRIM63, Master regulator of muscle mass. International Journal of Molecular Sciences, 21 (18), 6663, https://dx.doi.org/10.3390/ijms21186663,
• Polge C*, Cabantous S., Deval C., Claustre A., Hauvette A., Bouchenot C., Aniort J., Bechet D.,Combaret L., Attaix D., Taillandier D. (2018). A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate. Journal of Cachexia, Sarcopenia and Muscle, 1 (1), 129-145, (*first and corresponding author) https://dx.doi.org/10.1002/jcsm.12249.

PubMed (C. Polge) : https://pubmed.ncbi.nlm.nih.gov/?term=cecile+polge&sort=pubdate&size=100

ResearchGate : https://www.researchgate.net/profile/Cecile-Polge?ev=prf_overview