Study of the mechanisms of regulation of innate immunity dependent on HLH-30/TFEB-TFE3 by ubiquitin and ubiquitin-like proteins
Ubiquitination and ubiquitin-like modifications are conserved post-translational modifications (PTM) that can modulate protein stability, localization, or activity. These PTM are catalytically regulated by hundreds of E3 ligases, Deubiquitinating enzymes (DUB) and Ubiquitin-Like Peptidases (ULP) which modulate virtually all physiological processes. Innate immunity, which is the first line of defense against pathogens, makes no exception and dysregulation of E3/DUB and ULP gives rise to inflammatory and immune disorders. Recently, C. elegans HLH-30 and its mammalian homologues TFEB-TFE3 have emerged as major and conserved transcription immune factors. However, involvement of ubiquitination or ubiquitin-like modifications in the control of their activity as well as the host response they mediate have been poorly defined. We have used C. elegans model to undertake both RNAi screening and RNA-sequencing analysis and uncovered E3, DUB and ULP that regulate HLH-30 activity and/or host defense. Our current work and future projects aim at deciphering the mode of action of these enzymes, and whether they play a conserved role in TFEB-TFE3 dependent innate immunity using mammalian systems.
Innate Immunity, Ubiquitination, Sumoylation, Host Defence, Transcription Factor, C. elegans.
Dr Marcel DECKERT
Dr Nathalie PUJOL
Dr Guillaume BOSSIS
Dr Mehdi KHALED
Dr Christian BRAENDLE