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2018-09-20 - Colloque/Présentation - poster - Anglais - 1 page(s)

Claus Clothilde , Salvin Moriya, Tayri Tamar, Ansseau Eugénie , Decleves Anne-Emilie , Wilton Steve, Kalisman Nir, Coppée Frédérique , "Direct interaction of DUX4/4c with the multifunctional protein C1QBP in the pathology FSHD" in Structural Dynamics In Cellular Communication , Bruxelles, Belgique, 2018

  • Codes CREF : Biochimie (DI3112), Biologie moléculaire (DI3111)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Centre de Recherche UMONS-Ambroise Paré (UMHAP)
Texte intégral :

Abstract(s) :

(Anglais) Direct interaction of DUX4/4c with the multifunctional protein C1QBP in the pathology FSHD FSHD (FacioScapuloHumeral muscular Dystrophy) is one of the most common dystrophy. Our lab discovered the DUX4 (DoUble homeoboX4) causal gene that encodes a potent transcription factor. Misexpression of DUX4 in myoblasts interferes with many pathways leading to typical FSHD features.The DUX4c homologous gene is also overexpressed in FSHD muscles and could act as an FSHD modifier gene. Current therapeutic developments focus on the inhibition of DUX4 expression or activity. However, in view of DUX4 pleitotropic effects and time-limited expression, combinatory treatments might be developed. Therefore, a better understanding of the impact of DUX4/4c overexpression in healthy and pathological muscles is needed. For this purpose, our group identified DUX4/4c protein partners and surprisingly found a lot of RNA-binding as well as cytoplasmic proteins (Ansseau et al., 2016). To further confirm the specificity of these interactions and define the quaternary structures of DUX4/4c complexes, we now used cross-linking and mass-spectrometry to covalently capture DUX4/4c bound to their protein partners. Our first results are in keeping with our previous published data. Moreover, we found that C1QBP (complement component 1Q subcomponent-binding protein), a multifunctional and multicompartmental protein, interacts directly with DUX4c. Here, cross-links between C1QBP and DUX4c are found in two regions that are identical in DUX4. Given the known C1QBP functions, this interaction might participate to the FSHD pathology. The FSHD gain-of-function disease might probably need combined therapies. In that regard, we propose to target C1QBP or other DUX4 partner pathways. Our current perspective is to better decipher these pathways in FSH