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Accueil > Départements > Biologie des Génomes > Carmela GIGLIONE : Maturation des protéines, destinée cellulaire et thérapeutique

Carmela GIGLIONE : Présentation de l’équipe

Le groupe étudie les mécanismes fondamentaux, les rôles et l’impact sur le devenir des protéines des modifications cotraductionnelles N-terminaux essentiels, affectent la plupart des protéines procaryotes et eucaryotes. L’équipe affiche une activité parallèle sur des applications thérapeutiques. Nous sommes également équipe d’adossement de la plateforme de Spectrométrie de Masse dans le campus.

Thematics

It is recognized that the majority of proteins, to become functional actives, needs to undergo to several modifications which are most of the time catalyzed by specific enzymes. Until now, more than 400 different protein modifications have been identified. These modifications can be reversible or irreversible thus escorting the protein along its life cycle. N-terminal Protein Modifications (NPMs) correspond to a variety of chemical modifications occurring on most proteins when the protein is yet incomplete and still bound to the ribosome. They involve the N-terminal Methionine Excision process (NME) and acylations corresponding to N-α-acetylation (NTA) and N-Myristoylation (MYR) (Fig. 1).

Fig. 1 : The earliest modifications at the N-termini of proteins (NPMs).

These modifications can often be followed by further reversible modifications such phosphorylation or further acylation such as S-palmitoylation (PAL). All NPMs are essential for normal growth and function of any organism and affect a great number of proteins. NPMs are catalyzed by ubiquitous and essential enzymes being part of the so-called ribosome-associated protein biogenesis factors (RPBs), which are non-ribosomal proteins acting as soon as a nascent polypeptide reaches the extremity of the ribosomal exit tunnel. The interest of the scientific community for NPMs has been strongly revived during the past decade because i) genomics data have provided further insights in the enzymes involved in these modifications, ii) recent proteomics issues are now often turning to protein modifications and iii) natural or synthetic compounds targeting NPMs with antibiotic, antiparasitic, antifungal or anti-cancer effects have been discovered. Despite all that, it remains still a conundrum to understand why each of these modifications is so crucial for the life of all organisms. In this context, very few data exit also on how the enzymes involved in NPMs work on the ribosome for the sake of efficient and rapid translation of any nascent polypeptide chains and how these latter are supported by other protein biogenesis factors to ensure not only NPMs but also cotranslational folding and translocational mechanisms. To investigate these NPMs, the group develops an integrated strategy, involving reverse and chemical genomics, structural-proteomics approaches, bio-informatics and biochemical tools as well as cell biology analysis. Several prokaryotes and eukaryotes models are currently used in the lab and we take advantages of our knowledge to develop new inhibitors which could be used as pharmaceutical probes to investigate various pathologies or as new leads for potential therapeutic use.

Current research conducted in the lab is briefly outlined below :
1) INVESTIGATION OF THE ROLE(S) OF CYTOPLASMIC NME IN CANCER CELLS.
2) INVESTIGATION OF NME INHIBITORS BY SETTING A NEW STRUCTURAL PLATFORM RESULTING FROM THE COMBINATION OF SUPRAMOLECULAR MASS SPECTROMETRY, ENZYMOLOGY AND CRISTALLOGRAPHY.
3) DYNAMIC INTERACTION OF NPM ENZYMES WITH RIBOSOME.
4) PLANT-SPECIFIC N-MYRISTOYLATED TARGETS.
5) INTEGRATED AND FUNCTIONAL APPROACHES OF S-PALMITOYLATED AN N-MYRISTOYLATED PROTEOMES.
6) EXPLORING N-α-ACETYLATION IN PLANTS.
7) IMPROVEMENT OF PREDICTION TOOLS FOR NPMs.
8) CHARACTERIZATION OF NPMs IN RESPONSE TO BIOTIC AN ABIOTIC STRESSES.

Mots-clés

Cotranslational protein modifications, Deformylation, N-terminal Methionine Excision, Myristoylation, N-α-Acetylation, Palmytoylation, Ribosome, Antibacterial and anticancer agents, Comparative and Structural proteomics, protein fate

Contact


GIGLIONE Carmela [Directeur de Recherche - CNRS]
Equipe Giglione C. - Maturation des protéines, destinée cellulaire et thérapeutique [Responsable]
01 69 82 46 44 Gif - Bât 21

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