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Cécile Polge

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Presentation

**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).

Publications

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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 Loizon et al.
Cells, 2021, 10 (8), pp.1873. ⟨10.3390/cells10081873⟩
Journal articles hal-03314541v1
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Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control

Dulce Peris-Moreno , Laura Cussonneau , Lydie Combaret , Cécile Polge , Daniel Taillandier et al.
Molecules, 2021, 26 (2), pp.407. ⟨10.3390/molecules26020407⟩
Journal articles hal-03182261v1

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-Gandilhon et al.
Cells, 2021, 10 (8), pp.1974. ⟨10.3390/cells10081974⟩
Journal articles hal-03314544v1

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. Bechet et al.
International Journal of Molecular Sciences, 2020, 21 (10), pp.3691. ⟨10.3390/ijms21103691⟩
Journal articles hal-02935975v1
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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⟩
Journal articles hal-02952557v1

Skeletal muscle atrogenes: from rodent models to human pathologies

Daniel Taillandier , Cécile Polge
Journal articles hal-02192519v1

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 Polge et al.
Magnesium Research, 2019, 32 (3), pp.72-82. ⟨10.1684/mrh.2019.0458⟩
Journal articles hal-02520159v1
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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 Polge et al.
Journal of Cachexia, Sarcopenia and Muscle, 2019, 10 (2), pp.323-337. ⟨10.1002/jcsm.12376⟩
Journal articles hal-02167448v1
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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-Gandilhon et al.
Cells, 2018, 7 (12), ⟨10.3390/cells7120242⟩
Journal articles hal-02622197v1

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 Hauvette et al.
Journal of Cachexia, Sarcopenia and Muscle, 2018, 1 (1), pp.129-145. ⟨10.1002/jcsm.12249⟩
Journal articles hal-01730002v1
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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-Gandilhon et al.
Cells, 2018, 7 (11), ⟨10.3390/cells7110214⟩
Journal articles hal-01958290v1
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UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes

Cécile Polge , Roza Leulmi , Marianne Jarzaguet , Agnes Claustre , Lydie Combaret et al.
Journal of Cachexia, Sarcopenia and Muscle, 2016, 7 (3), pp.377-87. ⟨10.1002/jcsm.12060⟩
Journal articles hal-02633728v1
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Docosahexaenoic acid-supplementation prior to fasting prevents muscle atrophy in mice

Christiane Deval , Frédéric Capel , Brigitte Laillet , Cécile Polge , Daniel Bechet et al.
Journal of Cachexia, Sarcopenia and Muscle, 2016, 7 (5), pp.587-603. ⟨10.1002/jcsm.12103⟩
Journal articles hal-01512083v1

UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension

Cécile Polge , Nathalie Koulmann , Agnes Claustre , Marianne Jarzaguet , Bernard Serrurier et al.
International Journal of Biochemistry and Cell Biology, 2016, 79, pp.488-493. ⟨10.1016/j.biocel.2016.06.019⟩
Journal articles hal-01512230v1

Lower skeletal muscle capillarization in hypertensive elderly men

Marine Gueugneau , Cécile Coudy-Gandilhon , Bruno Meunier , Lydie Combaret , Daniel Taillandier et al.
Experimental Gerontology, 2016, 76, pp.80-88. ⟨10.1016/j.exger.2016.01.013⟩
Journal articles hal-01297805v1

Upregulation of MuRF1 and MAFbx participates to muscle wasting upon gentamicin-induced acute kidney injury

Julien Aniort , Cécile Polge , Agnes Claustre , Lydie Combaret , Daniel Bechet et al.
International Journal of Biochemistry and Cell Biology, 2016, 79, pp.505-516. ⟨10.1016/j.biocel.2016.04.006⟩
Journal articles hal-01512019v1
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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⟩
Journal articles 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 Théron , Bruno Meunier , Christiane Barboiron et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2015, 70 (5), pp.566-576. ⟨10.1093/gerona/glu086⟩
Journal articles hal-01812812v1
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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 Polge et al.
Journal of Cachexia, Sarcopenia and Muscle, 2015, 6 (1), pp.73-83. ⟨10.1002/jcsm.12011⟩
Journal articles hal-01901485v1
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Proteomics of muscle chronological ageing in post-menopausal women

Marine Gueugneau , Cecile Coudy-Gandilhon , Ophelie Gourbeyre , Christophe Chambon , Lydie Combaret et al.
BMC Genomics, 2014, 15 (1165), pp.1165. ⟨10.1186/1471-2164-15-1165⟩
Journal articles hal-01543975v1
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Apoptosis in capillary endothelial cells in ageing skeletal muscle

Huijuan Wang , Anne Listrat , Bruno Meunier , Marine Gueugneau , Cécile C. Coudy-Gandilhon et al.
Aging Cell, 2014, 13 (2), pp.254-262. ⟨10.1111/acel.12169⟩
Journal articles hal-02636978v1
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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 Ramirez et al.
PLoS ONE, 2013, 8 (5), pp.e62497. ⟨10.1371/journal.pone.0062497⟩
Journal articles hal-01987684v1

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-Schiltz et al.
International Journal of Biochemistry and Cell Biology, 2013, 45 (10), pp.2136-2146. ⟨10.1016/j.biocel.2013.05.031⟩
Journal articles hal-02502779v1

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 Meunier et al.
AJP - Endocrinology and Metabolism, 2012, 303 (11), pp.E1335 - E1347. ⟨10.1152/ajpendo.00379.2012⟩
Journal articles hal-02651117v1
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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 Brunisholz et al.
Journal of Proteomics, 2012, 75 (11), pp.3304-13. ⟨10.1016/j.jprot.2012.03.040⟩
Journal articles 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 Claustre et al.
FASEB Journal, 2011, 25 (11), pp.3790-3802. ⟨10.1096/fj.11-180968⟩
Journal articles hal-02420104v1
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Voies protéolytiques du muscle : oeuvres solistes ou ensemble orchestré ?

Lydie Combaret , Daniel Béchet , Daniel Taillandier , Cécile Polge , Didier Attaix et al.
Les Cahiers de Myologie, 2011, 4, pp.10-12
Journal articles hal-03318545v1
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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 Walling et al.
Journal of Biological Chemistry, 2009, 284 (51), pp.35412-24. ⟨10.1074/jbc.M109.035394⟩
Journal articles hal-00483927v1

Mitochondrial kinases and their molecular interaction with cardiolipin.

Uwe Schlattner , Malgorzata Tokarska-Schlattner , Sacnicte Ramirez , Anna Brückner , Laurence Kay et al.
Biochimica et Biophysica Acta - Molecular Cell Research, 2009, 1788 (10), pp.2032-47. ⟨10.1016/j.bbamem.2009.04.018⟩
Journal articles inserm-00422473v1

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. Konarev et al.
Journal of Biological Chemistry, 2009, 284 (40), pp.27425-37. ⟨10.1074/jbc.M109.047670⟩
Journal articles inserm-00422467v1
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Yeast two-hybrid, a powerful tool for systems biology.

Anna Brückner , Cécile Polge , Nicolas Lentze , Daniel Auerbach , Uwe Schlattner et al.
International Journal of Molecular Sciences, 2009, 10 (6), pp.2763-88. ⟨10.3390/ijms10062763⟩
Journal articles inserm-00422470v1

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 et al.
Plant Physiology, 2008, 148 (3), pp.1570-1582. ⟨10.1104/pp.108.123026⟩
Journal articles hal-03314679v1
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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 Galtier et al.
Planta, 2008, 227 (3), pp.625 - 639. ⟨10.1007/s00425-007-0644-6⟩
Journal articles hal-00188302v1

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⟩
Journal articles 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 Bouly et al.
Plant Physiology, 2006, 142 (3), pp.931-944. ⟨10.1104/pp.106.087718⟩
Journal articles 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 Kreis et al.
Plant Molecular Biology, 2004, 56 (5), pp.747-759. ⟨10.1007/s11103-004-5111-1⟩
Journal articles hal-03314592v1