Etude de la localisation cellulaire et du rôle de la protéine YopM de Yersinia enterocolitica
(2003)
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- Authors
- Supervisors
- Cornélis, Guy R.
- Abstract
- Upon contact with host cells, bacteria from Yersinia genus deliver six virulence proteins, termed Yops, into the host cell cytoplasm via a secretion mechanism called type III secretion. Of these six Yop, YopM is the only one for which neither a target nor an activity has been identified so far. It is neverthless essential for full virulence of Yersinia in mice. YopM is a very acidic protein that belongs to the leucine-rich repeat (LRR) structural family of proteins. Unlike the other Yops, which are highly conserved among the human-pathogenic yersiniae, YopM shows considerable heterogeneity in the number of LRRs. YopM was recently shown to accumulate in the nuclei of target eukaryotic cells by a mechanism that requires vesicular trafficking. YopM does not contain a sequence ressembling a known nuclear localization signal (NLS) for the regulated entry via nuclear pores. Using a yeast approach, we observed that the 32 C-terminal residues of YopM (C-ter) act as a NLS (publication1). This C-ter does not resemble any classical NLS. The C-ter was shown to direct large recombinant proteins into the nucleus of mammalian cells. The property of this domain was retained in yeast mutants affected in seven different known karyopherins. Thus we conclude that YopM reaches the nucleus by a mechanism independent of any known karyopherin (publication1). An analysis of the transcriptome of infected macrophages has shown that YopM influences the transcription of macrophage genes including B-myb. Here, we confirmed that YopM down-regulates the expression of B-myb in cells that were transfected with yopM or infected with Y.enterocolitica injecting YopM (unpublished results). We therefore conclude that migration to the nucleus is a pre-requisite for the inhibition of transcription of B-myb. The most likely hypothesis to explain the action of YopM is that YopM interacts with a transcriptional regulator. A two-hybrid screen conducted to identify an hypothetical partner turned out to be not conclusive because of a very high number of hits, attributable to the LRRs (unpublished results) . As an annex to this thesis, the role of YopP in apoptosis is presented (publication 2).
- Affiliations
Citations
Benabdillah, R. (2003). Etude de la localisation cellulaire et du rôle de la protéine YopM de Yersinia enterocolitica. https://hdl.handle.net/2078.5/110753