Know more

Our use of cookies

Cookies are a set of data stored on a user’s device when the user browses a web site. The data is in a file containing an ID number, the name of the server which deposited it and, in some cases, an expiry date. We use cookies to record information about your visit, language of preference, and other parameters on the site in order to optimise your next visit and make the site even more useful to you.

To improve your experience, we use cookies to store certain browsing information and provide secure navigation, and to collect statistics with a view to improve the site’s features. For a complete list of the cookies we use, download “Ghostery”, a free plug-in for browsers which can detect, and, in some cases, block cookies.

Ghostery is available here for free: https://www.ghostery.com/fr/products/

You can also visit the CNIL web site for instructions on how to configure your browser to manage cookie storage on your device.

In the case of third-party advertising cookies, you can also visit the following site: http://www.youronlinechoices.com/fr/controler-ses-cookies/, offered by digital advertising professionals within the European Digital Advertising Alliance (EDAA). From the site, you can deny or accept the cookies used by advertising professionals who are members.

It is also possible to block certain third-party cookies directly via publishers:

Cookie type

Means of blocking

Analytical and performance cookies

Realytics
Google Analytics
Spoteffects
Optimizely

Targeted advertising cookies

DoubleClick
Mediarithmics

The following types of cookies may be used on our websites:

Mandatory cookies

Functional cookies

Social media and advertising cookies

These cookies are needed to ensure the proper functioning of the site and cannot be disabled. They help ensure a secure connection and the basic availability of our website.

These cookies allow us to analyse site use in order to measure and optimise performance. They allow us to store your sign-in information and display the different components of our website in a more coherent way.

These cookies are used by advertising agencies such as Google and by social media sites such as LinkedIn and Facebook. Among other things, they allow pages to be shared on social media, the posting of comments, and the publication (on our site or elsewhere) of ads that reflect your centres of interest.

Our EZPublish content management system (CMS) uses CAS and PHP session cookies and the New Relic cookie for monitoring purposes (IP, response times).

These cookies are deleted at the end of the browsing session (when you log off or close your browser window)

Our EZPublish content management system (CMS) uses the XiTi cookie to measure traffic. Our service provider is AT Internet. This company stores data (IPs, date and time of access, length of the visit and pages viewed) for six months.

Our EZPublish content management system (CMS) does not use this type of cookie.

For more information about the cookies we use, contact INRA’s Data Protection Officer by email at cil-dpo@inra.fr or by post at:

INRA
24, chemin de Borde Rouge –Auzeville – CS52627
31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

Menu Logo Principal logo Université Clermont Auvergne & associés

Human Nutrition Unit

Zone de texte éditable et éditée et rééditée

Cécile Polge

Cécile Polge's profile

POLGE Cecile
Field of research

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.

Research activities

Our works indicate that the Ubiquitin Proteasome System (UPS) is responsible for the breakdown of the major contractile proteins. The UPS is a highly complex and tightly regulated proteolytic system comprising hundreds of enzymes, and that play a crucial role in controlling skeletal muscle mass. We study the precise mechanisms responsible for this adaptation and the potential coordination of this proteolytic machinery with other proteolytic systems (i.e. the lysosomal and caspase pathways). We are also seeking for biomarkers of muscle wasting, particularly during sarcopenia, which is the age-dependent loss of skeletal muscle. 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.

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, 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, 2016a). We determined that UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension (Polge et al, 2016b). Using complementary approaches, we recently identified 5 E2 enzymes interacting with MuRF1 (E2E1, E2G1, E2J1, E2J2, and E2L3). We showed that telethonin, a newly identified MuRF1 substrate, governed the affinity between MuRF1 and E2E1 or E2J1 (Polge et al, 2017). 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.

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

Polge C, Cabantous S, Deval C, Claustre A, Hauvette A, Bouchenot C, Aniort J, Béchet D, Combaret L, Attaix D, Taillandier D. A muscle-specific MuRF1-E2 network requires stabilization of MuRF1-E2 complexes by telethonin, a newly identified substrate. J Cachexia Sarcopenia Muscle. 2017 doi.org/10.1002/jcsm.12249

Polge C, Leulmi R, Jarzaguet M, Claustre A, Combaret L, Béchet D, Heng AE, Attaix D, Taillandier D. UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes. J Cachexia Sarcopenia Muscle. 2016 Jun;7(3):377-87. doi: 10.1002/jcsm

Polge C, Koulmann N, Claustre A, Jarzaguet M, Serrurier B, Combaret L, Béchet D, Bigard X, Attaix D, Taillandier D. UBE2D2 is not involved in MuRF1-dependent muscle wasting during hindlimb suspension. Int J Biochem Cell Biol. 2016 Oct;79:488-493. doi: 10.1016/j.biocel.2016.06.019.

Polge C, Attaix D, Taillandier D. Role of E2-Ub-conjugating enzymes during skeletal muscle atrophy. Front Physiol. 2015 Mar 10;6:59. doi: 10.3389/fphys.2015.00059.  

Polge C, Heng AE, Jarzaguet M, Ventadour S, Claustre A, Combaret L, Béchet D,  Matondo M, Uttenweiler-Joseph S, Monsarrat B, Attaix D, Taillandier D. Muscle actin is polyubiquitinylated in vitro and in vivo and targeted for breakdown by the E3 ligase MuRF1. FASEB J. 2011 Nov;25(11):3790-802. doi: 10.1096/fj.11-180968.

Brückner A, Polge C, Lentze N, Auerbach D, Schlattner U. Yeast two-hybrid, a powerful tool for systems biology. Int J Mol Sci. 2009 Jun 18;10(6):2763-88. doi: 10.3390/ijms10062763. Review.

back