Cécile Polge

Présentation

Proteolysis plays a key role in controlling muscle growth and atrophy. However, the regulatory mechanisms by which nutrients, hormones and/or physical activity control proteolysis are still poorly understood. The Ubiquitin Proteasome System (UPS) is responsible for the breakdown of the major contractile proteins and is a highly complex and tightly regulated proteolytic system comprising hundreds of enzymes. Understanding the regulatory mechanisms that control muscle mass is compulsory to ultimately preserve muscle strength during aging and many pathological wasting conditions like cancers, infections, trauma, renal failure, etc. Therefore, our final goal is to propose new therapeutic approaches that may prevent or limit muscle loss in catabolic conditions and/or improve muscle recovery following atrophying situations. These studies are of obvious clinical interest for reducing the length of hospitalizations and for improving treatments efficiency, and thus should ultimately result in decreased health care costs. As a key player in muscle atrophy, the Ubiquitin Proteasome System (UPS) is a potential target for fighting against an exacerbated proteolysis. UPS substrates are labeled by a ubiquitin chain catalyzed by a coordinated enzymatic cascade E1-E2-E3. The polyubiquitinated proteins are then degraded by the 26S proteasome. The UPS regulates numerous cellular processes and the proteasome is common to all the proteins to be degraded. Thus, targeting the proteasome would inhibit the whole UPS-linked cellular protein degradation and would be highly toxic for cells. By contrast, E2-E3 couples (35 and &gt; 600 respectively) are responsible for UPS selectivity, the E3 ligase being responsible for the recognition of the substrate while the E2 defines the type of ubiquitin chain linked to the substrate. Thus, E2-E3 couples represent a more promising target for fighting against muscle atrophy.

Research activities We demonstrated that α-actin is a UPS substrate in cultured myotubes and in human biopsies. In addition, the muscle-specific E3 ligase MuRF1 targets the myofibrillar actin pool (Polge et al, FASEB J. 2011). We demonstrated that UBE2B, an E2 highly expressed in atrophying skeletal muscle, targets the cytoplasmic pool of actin for MuRF1-independent degradation, which suggests that different E2-E3 couples target distinct pools of actin (Polge et al, JCSM 2016a). We determined that UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension (Polge et al, IJBCB 2016b). Using complementary approaches, we recently identified five E2 enzymes interacting with MuRF1 (E2E1, E2G1, E2J1, E2J2, and E2L3) (Polge et al, JCSM 2018). We showed that telethonin, a newly identified MuRF1 substrate, governed the affinity between MuRF1 and E2E1 or E2J1 (Polge et al, JCSM 2018). We are currently studying the capacity of E2-MuRF1 duos to target the main contractile proteins (actin, myosin heavy chains, …) both in vitro and in vivo (Polge et al, Cells 2018). We routinely use in vitro approaches and various cellular (C2C12, L6, …), animal (rodents) and human (biopsies) catabolic models. We are specialized in protein-protein interaction studies using complementary approaches like yeast 2- and 3-hybrid and SPR (Biacore).

Publications

Article dans une revue (43)

Design and synthesis of first-in-class stapled peptides targeting the E3 ligase MuRF1 to potentially prevent muscle wasting Joëlle Vidal,Corentin Fournet,Marielle Blot,Dulce Peris-Moreno,Michèle Reboud-Ravauxet al. Results in Chemistry, 2026, 20, pp.102974. ⟨10.1016/j.rechem.2025.102974⟩ Article dans une revue hal-05422823v1
Structure predictions of MuRF 1‐ UBE2 complexes identify amino acid residues governing interaction selectivity for each MuRF 1‐ E2 pair Agnès Claustre,Mélodie Malige,Maëlys Macheton,Lydie Combaret,Etienne Lefaiet al. FEBS Journal, 2025, 292 (10), pp.2559-2577. ⟨10.1111/febs.70017⟩ Article dans une revue hal-04993910v1
Tripartite Split‐GFP for High Throughput Screening of Small Molecules: A Powerful Strategy for Targeting Transient/Labile Interactors like E2‐E3 Ubiquitination Enzymes Cécile Polge,Stéphanie Cabantous,Daniel Taillandier ChemBioChem, 2024, 25 (6), pp.e202300723. ⟨10.1002/cbic.202300723⟩ Article dans une revue hal-04651502v1
Knockout of the muscle-specific E3 ligase MuRF1 affects liver lipid metabolism upon dexamethasone treatment in mice Laurent Mosoni,Arno Germond,Cécile Coudy-Gandilhon,Mélodie Malige,Agnès Claustreet al. ACS Omega, 2024, 9 (45), pp.45610-45623. ⟨10.1021/acsomega.4c08501&ref=pdf⟩ Article dans une revue hal-04766081v1
Induction of ATF4-Regulated Atrogenes Is Uncoupled from Muscle Atrophy during Disuse in Halofuginone-Treated Mice and in Hibernating Brown Bears Laura Cussonneau,Cécile Coudy-Gandilhon,Christiane Deval,Ghita Chaouki,Mehdi M. Djelloul-Mazouzet al. International Journal of Molecular Sciences, 2023, 24 (1), pp.621. ⟨10.3390/ijms24010621⟩ Article dans une revue hal-04178468v1
A Single Bout of Ultra-Endurance Exercise Reveals Early Signs of Muscle Aging in Master Athletes Cécile Coudy-Gandilhon,Marine Gueugneau,Christophe Chambon,Daniel Taillandier,Lydie Combaretet al. International Journal of Molecular Sciences, 2022, 23 (7), pp.3713. ⟨10.3390/ijms23073713⟩ Article dans une revue hal-03776164v1
UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin Dulce Peris-Moreno,Mélodie Malige,Agnès Claustre,Andrea Armani,Cécile Coudy-Gandilhonet al. Cells, 2021, 10 (8), pp.1974. ⟨10.3390/cells10081974⟩ Article dans une revue hal-03435380v1
Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men Marine Gueugneau,Cécile Coudy-Gandilhon,Christophe Chambon,Julien Verney,Daniel Taillandieret al. International Journal of Molecular Sciences, 2021, 22 (8), pp.4205. ⟨10.3390/ijms22084205⟩ Article dans une revue hal-03238377v1
Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear Laura Cussonneau,Christian Boyer,Charlotte Brun,Christiane Deval,Emmanuelle Loizonet al. Cells, 2021, 10 (8), pp.1873. ⟨10.3390/cells10081873⟩ Article dans une revue hal-03314541v1
Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control Dulce Peris-Moreno,Laura Cussonneau,Lydie Combaret,Cécile Polge,Daniel Taillandier Molecules, 2021, 26 (2), pp.407. ⟨10.3390/molecules26020407⟩ Article dans une revue (article de synthèse) hal-03182261v1
Mitophagy and mitochondria biogenesis are differentially induced in rat skeletal muscles during immobilization and/or remobilization Christiane Deval,Julie Calonne,Cécile Coudy-Gandilhon,Emilie Vazeille,Daniel D. Bechetet al. International Journal of Molecular Sciences, 2020, 21 (10), pp.3691. ⟨10.3390/ijms21103691⟩ Article dans une revue hal-02935975v2
MuRF1/TRIM63, Master regulator of muscle mass Dulce Peris-Moreno,Daniel Taillandier,Cécile Polge International Journal of Molecular Sciences, 2020, 21 (18), pp.6663. ⟨10.3390/ijms21186663⟩ Article dans une revue hal-02952557v1
Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work Julien Aniort,Alexandre Stella,Carole Philipponnet,Anaïs Poyet,Cécile Polgeet al. Journal of Cachexia, Sarcopenia and Muscle, 2019, 10 (2), pp.323-337. ⟨10.1002/jcsm.12376⟩ Article dans une revue hal-02167448v1
Magnesium transport and homeostasis-related gene expression in skeletal muscle of young and old adults: analysis of the transcriptomic data from the PROOF cohort Study. Cécile Coudy-Gandilhon,Marine Gueugneau,Daniel Taillandier,Lydie Combaret,Cécile Polgeet al. Magnesium Research, 2019, 32 (3), pp.72-82. ⟨10.1684/mrh.2019.0458⟩ Article dans une revue hal-02520159v1
Skeletal muscle atrogenes: from rodent models to human pathologies Daniel Taillandier,Cécile Polge Biochimie, 2019, 166, ⟨10.1016/j.biochi.2019.07.014⟩ Article dans une revue (article de synthèse) hal-02192519v1
A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate Cécile Polge,Stéphanie Cabantous,Christiane Deval,Agnes Claustre,Antoine Hauvetteet al. Journal of Cachexia, Sarcopenia and Muscle, 2018, 1 (1), pp.129-145. ⟨10.1002/jcsm.12249⟩ Article dans une revue hal-01730002v1
UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment Cécile Polge,Julien Aniort,Andrea Armani,Agnes Claustre,Cécile Coudy-Gandilhonet al. Cells, 2018, 7 (11), ⟨10.3390/cells7110214⟩ Article dans une revue hal-01958290v1
UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment (vol 7, 214, 2018) Cécile Polge,Julien Aniort,Andrea Armani,Agnes Claustre,Cécile Coudy-Gandilhonet al. Cells, 2018, 7 (12), ⟨10.3390/cells7120242⟩ Article dans une revue hal-02622197v1
Upregulation of MuRF1 and MAFbx participates to muscle wasting upon gentamicin-induced acute kidney injury Julien Aniort,Cécile Polge,Agnes Claustre,Lydie Combaret,Daniel Bechetet al. International Journal of Biochemistry and Cell Biology, 2016, 79, pp.505-516. ⟨10.1016/j.biocel.2016.04.006⟩ Article dans une revue hal-01512019v1
UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension Cécile Polge,Nathalie Koulmann,Agnes Claustre,Marianne Jarzaguet,Bernard Serrurieret al. International Journal of Biochemistry and Cell Biology, 2016, 79, pp.488-493. ⟨10.1016/j.biocel.2016.06.019⟩ Article dans une revue hal-01512230v1
Docosahexaenoic acid-supplementation prior to fasting prevents muscle atrophy in mice Christiane Deval,Frédéric Capel,Brigitte Laillet,Cécile Polge,Daniel Bechetet al. Journal of Cachexia, Sarcopenia and Muscle, 2016, 7 (5), pp.587-603. ⟨10.1002/jcsm.12103⟩ Article dans une revue hal-01512083v1
UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes Cécile Polge,Roza Leulmi,Marianne Jarzaguet,Agnes Claustre,Lydie Combaretet al. Journal of Cachexia, Sarcopenia and Muscle, 2016, 7 (3), pp.377-87. ⟨10.1002/jcsm.12060⟩ Article dans une revue hal-02633728v1
Lower skeletal muscle capillarization in hypertensive elderly men Marine Gueugneau,Cécile Coudy-Gandilhon,Bruno Meunier,Lydie Combaret,Daniel Taillandieret al. Experimental Gerontology, 2016, 76, pp.80-88. ⟨10.1016/j.exger.2016.01.013⟩ Article dans une revue istex hal-01297805v1
Role of E2-Ub-conjugating enzymes during skeletal muscle atrophy Cécile Polge,Didier Attaix,Daniel Taillandier Frontiers in Physiology, 2015, 6, n.p. ⟨10.3389/fphys.2015.00059⟩ Article dans une revue (article de synthèse) hal-02639857v1
Skeletal muscle lipid content and oxidative activity in relation to muscle fiber type in aging and metabolic syndrome Marine Gueugneau,Cécile Coudy-Gandilhon,Laetitia Theron,Bruno Meunier,Christiane Barboironet al. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2015, 70 (5), pp.566-576. ⟨10.1093/gerona/glu086⟩ Article dans une revue hal-01812812v1
The delayed recovery of the remobilized rat tibialis anterior muscle reflects a defect in proliferative and terminal differentiation that impairs early regenerative processes Lamia Slimani,Emilie Vazeille,Christiane Deval,Bruno Meunier,Cécile Polgeet al. Journal of Cachexia, Sarcopenia and Muscle, 2015, 6 (1), pp.73-83. ⟨10.1002/jcsm.12011⟩ Article dans une revue hal-01901485v1
Apoptosis in capillary endothelial cells in ageing skeletal muscle Huijuan Wang,Anne Listrat,Bruno Meunier,Marine Gueugneau,Cécile C. Coudy-Gandilhonet al. Aging Cell, 2014, 13 (2), pp.254-262. ⟨10.1111/acel.12169⟩ Article dans une revue hal-02636978v1
Proteomics of muscle chronological ageing in post-menopausal women Marine Gueugneau,Cecile Coudy-Gandilhon,Ophelie Gourbeyre,Christophe Chambon,Lydie Combaretet al. BMC Genomics, 2014, 15 (1165), pp.1165. ⟨10.1186/1471-2164-15-1165⟩ Article dans une revue hal-01543975v1
Deciphering the ubiquitin proteome: Limits and advantages of high throughput global affinity purification-mass spectrometry approaches Cécile Polge,Sandrine Uttenweiler-Joseph,Roza Leulmi,Anne-Elisabeth Heng,Odile Burlet-Schiltzet al. International Journal of Biochemistry and Cell Biology, 2013, 45 (10), pp.2136-2146. ⟨10.1016/j.biocel.2013.05.031⟩ Article dans une revue istex hal-02502779v1
Glutathione S-Transferases Interact with AMP-Activated Protein Kinase: Evidence for S-Glutathionylation and Activation In Vitro Anna Klaus,Sarah Zorman,Alexandre Berthier,Cécile Polge,Sacnicte Ramirezet al. PLoS ONE, 2013, 8 (5), pp.e62497. ⟨10.1371/journal.pone.0062497⟩ Article dans une revue hal-01987684v1
The worsening of tibialis anterior muscle atrophy during recovery post-immobilization correlates with enhanced connective tissue area, proteolysis, and apoptosis Lamia Slimani,Didier D. Micol,Julien Amat,Geoffrey Delcros,Bruno Meunieret al. AJP - Endocrinology and Metabolism, 2012, 303 (11), pp.E1335 - E1347. ⟨10.1152/ajpendo.00379.2012⟩ Article dans une revue hal-02651117v1
A two-dimensional screen for AMPK substrates identifies tumor suppressor fumarate hydratase as a preferential AMPKα2 substrate. Anna Klaus,Cécile Polge,Sarah Zorman,Yolanda Auchli,René Brunisholzet al. Journal of Proteomics, 2012, 75 (11), pp.3304-13. ⟨10.1016/j.jprot.2012.03.040⟩ Article dans une revue inserm-00696309v1
Muscle actin is polyubiquitinylated in vitro and in vivo and targeted for breakdown by the E3 ligase MuRF1 Cécile Polge,Anne-Elisabeth Heng,Marianne Jarzaguet,Sophie Ventadour,Agnes Claustreet al. FASEB Journal, 2011, 25 (11), pp.3790-3802. ⟨10.1096/fj.11-180968⟩ Article dans une revue hal-02420104v1
Voies protéolytiques du muscle : oeuvres solistes ou ensemble orchestré ? Lydie Combaret,Daniel Béchet,Daniel Taillandier,Cécile Polge,Didier Attaix Les Cahiers de Myologie, 2011, 4, pp.10-12 Article dans une revue hal-03318545v1
Yeast two-hybrid, a powerful tool for systems biology. Anna Brückner,Cécile Polge,Nicolas Lentze,Daniel Auerbach,Uwe Schlattner International Journal of Molecular Sciences, 2009, 10 (6), pp.2763-88. ⟨10.3390/ijms10062763⟩ Article dans une revue inserm-00422470v1
Homo-oligomerization and activation of AMP-activated protein kinase are mediated by the kinase domain alphaG-helix. Roland Scholz,Marianne Suter,Théodore Weimann,Cécile Polge,Petr V. Konarevet al. Journal of Biological Chemistry, 2009, 284 (40), pp.27425-37. ⟨10.1074/jbc.M109.047670⟩ Article dans une revue inserm-00422467v1
Mitochondrial kinases and their molecular interaction with cardiolipin. Uwe Schlattner,Malgorzata Tokarska-Schlattner,Sacnicte Ramirez,Anna Brückner,Laurence Kayet al. Biochimica et Biophysica Acta - Molecular Cell Research, 2009, 1788 (10), pp.2032-47. ⟨10.1016/j.bbamem.2009.04.018⟩ Article dans une revue inserm-00422473v1
Evidence for the Existence in Arabidopsis thaliana of the Proteasome Proteolytic Pathway: ACTIVATION IN RESPONSE TO CADMIUM. Cécile Polge,Michel Jaquinod,Frances Holzer,Jacques Bourguignon,Linda Wallinget al. Journal of Biological Chemistry, 2009, 284 (51), pp.35412-24. ⟨10.1074/jbc.M109.035394⟩ Article dans une revue hal-00483927v1
Modifications in endopeptidase and 20S proteasome expression and activities in cadmium treated tomato (Solanum lycopersicum L.) plants Wahbi Djebali,Philippe Gallusci,Cécile Polge,Latifa Boulila,Nathalie Galtieret al. Planta, 2008, 227 (3), pp.625 - 639. ⟨10.1007/s00425-007-0644-6⟩ Article dans une revue istex hal-00188302v1
β -Subunits of the SnRK1 Complexes Share a Common Ancestral Function Together with Expression and Function Specificities; Physical Interaction with Nitrate Reductase Specifically Occurs via AKIN β 1-Subunit Cécile Polge,Mathieu Jossier,Pierre Crozet,Lionel Gissot,Martine Thomas Plant Physiology, 2008, 148 (3), pp.1570-1582. ⟨10.1104/pp.108.123026⟩ Article dans une revue hal-03314679v1
SNF1/AMPK/SnRK1 kinases, global regulators at the heart of energy control? Cécile Polge,Martine Thomas Trends in Plant Science, 2007, 12 (1), pp.20-8. ⟨10.1016/j.tplants.2006.11.005⟩ Article dans une revue istex hal-00154622v1
AKINbetagamma contributes to SnRK1 heterotrimeric complexes and interacts with two proteins implicated in plant pathogen resistance through its KIS/GBD sequence Lionel L. Gissot,Cécile Polge,Mathieu Jossier,Thomas Girin,Jean-Pierre Boulyet al. Plant Physiology, 2006, 142 (3), pp.931-944. ⟨10.1104/pp.106.087718⟩ Article dans une revue hal-02668884v1
AKINbeta3, a plant specific SnRK1 protein, is lacking domains present in yeast and mammals non-catalytic ?-subunits Cécile Polge,Lionel Gissot,Jean-Pierre Bouly,Thomas Lemaitre,Martin Kreiset al. Plant Molecular Biology, 2004, 56 (5), pp.747-759. ⟨10.1007/s11103-004-5111-1⟩ Article dans une revue istex hal-03314592v1

Autre publication scientifique (1)

L'actine, principale protéine contractile du muscle squelettique, est ciblée et dégradée par le système protéolytique ubiquitine-protéasome dépendant, dans des cellules et chez l'Homme Cécile Polge,Anne-Elisabeth Heng,A-E Heng,Marianne Jarzaguet,Sophie Ventadouret al. Recherche en Nutrition en Auvergne, Contribution du CRNH et de ses équipes de Recherche, 2013 Autre publication scientifique hal-03318523v1

Thèse (1)

Etude de la structure des complexes kinases AKIN chez A. thaliana ; expression et fonction des sous-unités de type beta Cécile Polge Sciences du Vivant [q-bio]. Université paris sud 11, 2004. Français. ⟨NNT : ⟩ Thèse tel-04652877v1

HDR (1)

Etude des mécanismes de dégradation des protéines myofibrillaires majeures du muscle squelettique - Rôle de la voie Ubiquitine Protéasome Dépendante Cécile Polge Alimentation et Nutrition. Université d'Auvergne - Clermont-Ferrand I, 2013 HDR tel-02807024v1