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31

Cécile Polge


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 > 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).


Journal articles30 documents

  • Christiane Deval, Julie Calonne, Cécile Coudy-Gandilhon, Emilie Vazeille, Daniel Bechet, et al.. Mitophagy and Mitochondria Biogenesis Are Differentially Induced in Rat Skeletal Muscles during Immobilization and/or Remobilization. International Journal of Molecular Sciences, MDPI, 2020, 21 (10), pp.3691. ⟨10.3390/ijms21103691⟩. ⟨hal-02935975⟩
  • Dulce Peris-Moreno, Daniel Taillandier, Cécile Polge. MuRF1/TRIM63, Master Regulator of Muscle Mass. International Journal of Molecular Sciences, MDPI, 2020, 21 (18), pp.6663. ⟨10.3390/ijms21186663⟩. ⟨hal-02952557⟩
  • Cécile Coudy-Gandilhon, Marine Gueugneau, Daniel Taillandier, Lydie Combaret, Cécile Polge, et al.. 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.. Magnesium Research, John Libbey Eurotext, 2019, 32 (3), pp.72-82. ⟨10.1684/mrh.2019.0458⟩. ⟨hal-02520159⟩
  • Daniel Taillandier, Cécile Polge. Skeletal muscle atrogenes: from rodent models to human pathologies. Biochimie, Elsevier, 2019, 166, ⟨10.1016/j.biochi.2019.07.014⟩. ⟨hal-02192519⟩
  • Julien Aniort, Alexandre Stella, Carole Philipponnet, Anaïs Poyet, Cécile Polge, et al.. Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work. Journal of Cachexia, Sarcopenia and Muscle, Wiley Open Access/Springer Verlag, 2019, 10 (2), pp.323-337. ⟨10.1002/jcsm.12376⟩. ⟨hal-02167448⟩
  • Cécile Polge, Julien Aniort, Andrea Armani, Agnes Claustre, Cécile Coudy-Gandilhon, et al.. 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). Cells, MDPI, 2018, 7 (12), ⟨10.3390/cells7120242⟩. ⟨hal-02622197⟩
  • Cécile Polge, Stéphanie Cabantous, Christiane Deval, Agnes Claustre, Antoine Hauvette, et al.. A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate.. Journal of Cachexia, Sarcopenia and Muscle, Wiley Open Access/Springer Verlag, 2018, 1 (1), pp.129-145. ⟨10.1002/jcsm.12249⟩. ⟨hal-01730002⟩
  • Cécile Polge, Julien Aniort, Andrea Armani, Agnes Claustre, Cécile Coudy-Gandilhon, et al.. UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment. Cells, MDPI, 2018, 7 (11), ⟨10.3390/cells7110214⟩. ⟨hal-01958290⟩
  • Cécile Polge, Nathalie Koulmann, Agnes Claustre, Marianne Jarzaguet, Bernard Serrurier, et al.. UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension. International Journal of Biochemistry and Cell Biology, Elsevier, 2016, 79, pp.488-493. ⟨10.1016/j.biocel.2016.06.019⟩. ⟨hal-01512230⟩
  • Cécile Polge, Roza Leulmi, Marianne Jarzaguet, Agnes Claustre, Lydie Combaret, et al.. UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes. Journal of Cachexia, Sarcopenia and Muscle, Wiley Open Access/Springer Verlag, 2016, 7 (3), pp.377-87. ⟨10.1002/jcsm.12060⟩. ⟨hal-02633728⟩
  • Julien Aniort, Cécile Polge, Agnes Claustre, Lydie Combaret, Daniel Bechet, et al.. Upregulation of MuRF1 and MAFbx participates to muscle wasting upon gentamicin-induced acute kidney injury. International Journal of Biochemistry and Cell Biology, Elsevier, 2016, 79, pp.505-516. ⟨10.1016/j.biocel.2016.04.006⟩. ⟨hal-01512019⟩
  • Christiane Deval, Frédéric Capel, Brigitte Laillet, Cécile Polge, Daniel Bechet, et al.. Docosahexaenoic acid-supplementation prior to fasting prevents muscle atrophy in mice. Journal of Cachexia, Sarcopenia and Muscle, Wiley Open Access/Springer Verlag, 2016, 7 (5), pp.587-603. ⟨10.1002/jcsm.12103⟩. ⟨hal-01512083⟩
  • Marine Gueugneau, Cécile Coudy-Gandilhon, Bruno Meunier, Lydie Combaret, Daniel Taillandier, et al.. Lower skeletal muscle capillarization in hypertensive elderly men. Experimental Gerontology, Elsevier, 2016, 76, pp.80-88. ⟨10.1016/j.exger.2016.01.013⟩. ⟨hal-01297805⟩
  • Cécile Polge, Didier Attaix, Daniel Taillandier. Role of E2-Ub-conjugating enzymes during skeletal muscle atrophy. Frontiers in Physiology, Frontiers, 2015, 6, n.p. ⟨10.3389/fphys.2015.00059⟩. ⟨hal-02639857⟩
  • Lamia Slimani, Emilie Vazeille, Christiane Deval, Bruno Meunier, Cécile Polge, et al.. The delayed recovery of the remobilized rat tibialis anterior muscle reflects a defect in proliferative and terminal differentiation that impairs early regenerative processes. Journal of Cachexia, Sarcopenia and Muscle, Wiley Open Access/Springer Verlag, 2015, 6 (1), pp.73-83. ⟨10.1002/jcsm.12011⟩. ⟨hal-01901485⟩
  • Marine Gueugneau, Cécile Coudy-Gandilhon, Laetitia Théron, Bruno Meunier, Christiane Barboiron, et al.. Skeletal muscle lipid content and oxidative activity in relation to muscle fiber type in aging and metabolic syndrome. Journals of Gerontology, Series A, Oxford University Press (OUP): Policy B - Oxford Open Option D, 2015, 70 (5), pp.566-576. ⟨10.1093/gerona/glu086⟩. ⟨hal-01812812⟩
  • Marine Gueugneau, Cecile Coudy-Gandilhon, Ophelie Gourbeyre, Christophe Chambon, Lydie Combaret, et al.. Proteomics of muscle chronological ageing in post-menopausal women. BMC Genomics, BioMed Central, 2014, 15 (1165), pp.1165. ⟨10.1186/1471-2164-15-1165⟩. ⟨hal-01543975⟩
  • Huijuan Wang, Anne Listrat, Bruno Meunier, Marine Gueugneau, Cécile Coudy-Gandilhon, et al.. Apoptosis in capillary endothelial cells in ageing skeletal muscle. Aging Cell, Wiley Open Access, 2014, 13 (2), pp.254-262. ⟨10.1111/acel.12169⟩. ⟨hal-02636978⟩
  • Anna Klaus, Sarah Zorman, Alexandre Berthier, Cécile Polge, Sacnicte Ramirez, et al.. Glutathione S-Transferases Interact with AMP-Activated Protein Kinase: Evidence for S-Glutathionylation and Activation In Vitro. PLoS ONE, Public Library of Science, 2013, 8 (5), pp.e62497. ⟨10.1371/journal.pone.0062497⟩. ⟨hal-01987684⟩
  • Cécile Polge, Sandrine Uttenweiler-Joseph, Roza Leulmi, Anne-Elisabeth Heng, Odile Burlet-Schiltz, et al.. Deciphering the ubiquitin proteome: Limits and advantages of high throughput global affinity purification-mass spectrometry approaches. The International Journal of Biochemistry & Cell Biology, 2013, 45 (10), pp.2136-2146. ⟨10.1016/j.biocel.2013.05.031⟩. ⟨hal-02502779⟩
  • Anna Klaus, Cécile Polge, Sarah Zorman, Yolanda Auchli, René Brunisholz, et al.. A two-dimensional screen for AMPK substrates identifies tumor suppressor fumarate hydratase as a preferential AMPKα2 substrate.. Journal of Proteomics, Elsevier, 2012, 75 (11), pp.3304-13. ⟨10.1016/j.jprot.2012.03.040⟩. ⟨inserm-00696309⟩
  • Lamia Slimani, Didier Micol, Julien Amat, Geoffrey Delcros, Bruno Meunier, et al.. The worsening of tibialis anterior muscle atrophy during recovery post-immobilization correlates with enhanced connective tissue area, proteolysis, and apoptosis. AJP - Endocrinology and Metabolism, American Physiological Society, 2012, 303 (11), pp.E1335 - E1347. ⟨10.1152/ajpendo.00379.2012⟩. ⟨hal-02651117⟩
  • Cécile Polge, Anne-Elisabeth Heng, Marianne Jarzaguet, Sophie Ventadour, Agnes Claustre, et al.. Muscle actin is polyubiquitinylated in vitro and in vivo and targeted for breakdown by the E3 ligase MuRF1. FASEB Journal, Federation of American Society of Experimental Biology, 2011, 25 (11), pp.3790-3802. ⟨10.1096/fj.11-180968⟩. ⟨hal-02420104⟩
  • Uwe Schlattner, Malgorzata Tokarska-Schlattner, Sacnicte Ramirez, Anna Brückner, Laurence Kay, et al.. Mitochondrial kinases and their molecular interaction with cardiolipin.. Biochimica et Biophysica Acta - Molecular Cell Research, Elsevier, 2009, 1788 (10), pp.2032-47. ⟨10.1016/j.bbamem.2009.04.018⟩. ⟨inserm-00422473⟩
  • Cécile Polge, Michel Jaquinod, Frances Holzer, Jacques Bourguignon, Linda Walling, et al.. Evidence for the Existence in Arabidopsis thaliana of the Proteasome Proteolytic Pathway: ACTIVATION IN RESPONSE TO CADMIUM.: Activation in response to cadmium. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (51), pp.35412-24. ⟨10.1074/jbc.M109.035394⟩. ⟨hal-00483927⟩
  • Roland Scholz, Marianne Suter, Théodore Weimann, Cécile Polge, Petr Konarev, et al.. Homo-oligomerization and activation of AMP-activated protein kinase are mediated by the kinase domain alphaG-helix.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (40), pp.27425-37. ⟨10.1074/jbc.M109.047670⟩. ⟨inserm-00422467⟩
  • Anna Brückner, Cécile Polge, Nicolas Lentze, Daniel Auerbach, Uwe Schlattner. Yeast two-hybrid, a powerful tool for systems biology.. International Journal of Molecular Sciences, MDPI, 2009, 10 (6), pp.2763-88. ⟨10.3390/ijms10062763⟩. ⟨inserm-00422470⟩
  • Wahbi Djebali, Philippe Gallusci, Cécile Polge, Latifa Boulila, Nathalie Galtier, et al.. Modifications in endopeptidase and 20S proteasome expression and activities in cadmium treated tomato (Solanum lycopersicum L.) plants. Planta, Springer Verlag, 2008, 227 (3), pp.625 - 639. ⟨10.1007/s00425-007-0644-6⟩. ⟨hal-00188302⟩
  • Cécile Polge, Martine Thomas. SNF1/AMPK/SnRK1 kinases, global regulators at the heart of energy control?. Trends in Plant Science, Elsevier, 2007, 12 (1), pp.20-8. ⟨10.1016/j.tplants.2006.11.005⟩. ⟨hal-00154622⟩
  • Lionel Gissot, Cécile Polge, Mathieu Jossier, Thomas Girin, Jean-Pierre Bouly, et al.. AKINbetagamma contributes to SnRK1 heterotrimeric complexes and interacts with two proteins implicated in plant pathogen resistance through its KIS/GBD sequence. Plant Physiology, American Society of Plant Biologists, 2006, 142 (3), pp.931-944. ⟨10.1104/pp.106.087718⟩. ⟨hal-02668884⟩

Habilitation à diriger des recherches1 document

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