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Interactomic map of the Ets factors family : Identification of unexpected functions in mRNA processing
Rambout, Xavier; Simonis, Nicolas; Demoitié, Pauline et al.
2012In Keystone symposium - Protein-RNA Interactions in Biology and Disease (C1)
Peer reviewed
 

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Abstract :
[en] The Ets factors are a family of 27 transcription factors characterized by their unique DNA-binding domain, the ETS domain. We aimed at building a protein-protein interaction (PPI) map (interactome) of the human Ets factors in order to better define their roles and regulations in normal and oncogenic processes. The Ets interactome was built on a high-throughput yeast-two hybrid (Y2H) approach, and a literature and database curation of confident interactions which led us to the identification of 602 PPIs and 369 different protein partners. Clusterization using the Network Analysis Tool box (NeAT) divided the ETS interactome into 39 functional sub-networks. Among these, we identified Cluster16 as highly connected to the Erg ETS subfamily. A gene ontology (GO) enrichment analysis revealed that Cluster16 was associated to various aspects of mRNA processing. We therefore hypothesized that Erg factors might have a role in post-transcriptional gene regulation. This would constitute a entirely new and undisclosed role for ETS factors, which are so far firmly established as transcription factors. In support of our hypothesis, we observed that ERG localized in p-bodies, cytoplasmic sites of mRNA decay. Interestingly, under various cellular stresses, a portion of ERG and its partners from Cluster16 localized in stress granules, cytoplasmic sites of mRNA silencing physically linked to p-bodies. Hence, we hypothesized that Erg proteins might be involved in cellular mRNAs degradation. To test this, we performed a MS2-based tethering assay and showed that the recruit-ment of Erg factors promoted degradation of a reporter mRNA, mainly via its N-ter domain. Very importantly, oncogenic TET-Erg fusions described in AML and Ewing’s sarcoma exhibited diminished ability to degrade target mRNAs, concomitantly with the loss of the N-ter domain of the corresponding Erg protein. This re-inforces the important role of Erg proteins in mRNA degradation in cancer. Our efforts are now concentrated on identifying the molecular determinants behind this new function of Erg proteins.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rambout, Xavier ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Simonis, Nicolas
Demoitié, Pauline
Cherkaoui, Majid ;  Université de Liège - ULiège > GIGA-Research
Lebrun, Marielle  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Vidal, Marc
Kruys, Véronique
Twizere, Jean-Claude  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Dequiedt, Franck  ;  Université de Liège - ULiège > GIGA-Research
Language :
English
Title :
Interactomic map of the Ets factors family : Identification of unexpected functions in mRNA processing
Publication date :
05 March 2012
Event name :
Keystone Symposium : Protein-RNA interactions in Biology and Disease
Event organizer :
Tuschl, Thomas
Event place :
Santa Fe, United States
Event date :
du 4 mars 2012 au 9 mars 2012
Audience :
International
Main work title :
Keystone symposium - Protein-RNA Interactions in Biology and Disease (C1)
Peer reviewed :
Peer reviewed
Name of the research project :
Establishment of an interactomic map of the Ets factors family: Towards a better understanding of their roles in oncogenic processes
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
Fondation contre le Cancer [BE]
Available on ORBi :
since 12 March 2012

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