Scientific topics
Keywords
ITMO
Pierre Lutz PhD Molecular and Cellular Biology
Course and current status
CIVIL STATUS
Name: Pierre G. Lutz
Date of birth: October 3rd, 1967
Nationality: French
Familial status: Married, 2 children
Laboratory:
Address: Infinity, Toulouse Institute for Infectious and Inflammatory Diseases / Institut Toulousain des Maladies Infectieuses et Inflammatoires
INSERM UMR1291 - CNRS UMR5051 - Université Toulouse III, CHU Purpan, F-31024 Toulouse Cedex 3, France
Phone: +33 (0) 5 62 74 83 88
e-mail: Pierre.Lutz@inserm.fr
web: https://www.infinity.inserm.fr/en/research-teams/equipe-10-r-lesourne/
CURRENT POSITION
CNRS, Directeur de Recherche (since October 2009)
INDEPENDENT POSITIONS
2020: Principal Investigator “Ubiquitin enzymes in immunity and disease”, Infinity, INSERM – CNRS – UPS, Toulouse (France); director: Dr. Nicolas Fazilleau. Integrative Mapping of Lymphocyte Signaling and Function Team (Renaud Lesourne and Loïc Dupré)
2006-June 2020: Group leader, Institute of Pharmacology and Structural Biology, CNRS – UPS, Toulouse (France); directors: Prof. François Amalric and Dr. Jean-Philippe Girard
Jan-July 2005: Group leader, Institut Cochin, INSERM U567, CNRS UMR8104, Univ. R. Descartes, Paris (France); director: Prof. Axel Kahn
2003-2004: Group leader, INSERM U417, Paris (France); director: Prof. Yvon E. Cayre
2000-2002: Permanent position at the CNRS (Chargé de Recherche 1ère classe)
RESEARCH TRAINING
1996-2000: Post-doctoral fellow, INSERM U417, Paris (France), director Prof. Yvon E. Cayre
1992-1996: PhD, Molecular Biology, supervisor Prof. Claude Kedinger. IGBMC; director Prof. Pierre Chambon, Illkirch (France)
ADDITIONAL TRAINING
1992: Scientifique du Contingent (French military duties), INSERM U338, Strasbourg (France); director Dr. Dominique Aunis
DEGREES AND DIPLOMA
2003: Habilitation à diriger des recherches, Paris VII University
1992-1996: PhD, Molecular Biology, obtained with highest honors (supervisor Prof. Claude Kedinger). Louis Pasteur University, Strasbourg; IGBMC, director Prof. Pierre Chambon, Illkirch (France).
1991: Agrégation de Biochimie-Génie Biologique
DISTINCTIONS-MEMBERSHIPS
Lauréat 2023 de la Fondation du Souffle – Promotion Marina Pretolani
Recipient of the Sanofi Innovation Awards Europe 2020
PUBLICATIONS
Maire K, Chamy L, Ghazali S, Carratala-Lasserre M, Zahm M, Bouisset C, Métais A, Combes-Soia L, de la Fuente-Vizuete L, Trad H, Savignac M, Gonzalez de Peredo A, Subramaniam A, Joffre O, Lutz PG* and Lamsoul I* (2024) Fine-Tuning Levels of Filamins a and b as a Specific Mechanism Sustaining Th2 Lymphocyte Functions. Nature Communications, 15:10574. (*: contributed equally to the work).
Lamsoul, I., Dupré, L and Lutz, P.G. (2020) Molecular tuning of Filamin A cellular concentration as a gatekeeper to integrin activation [invited review]. Frontiers in Cell and Developmental Biology, 8:1432.
Yamak, A., Hu, D., Mittal, N., Buikema, J.W., Ditta, S., Lutz, P.G., Moog-Lutz, C., Ellinor, P.T. and Domian, I.J. Loss of Asb2 impairs cardiomyocyte differentiation and leads to congenital double outlet right ventricle (2020). iScience. 23:100959.
Spinner, C.A., Lamsoul, I., Métais, A., Febrissy, C., Moog-Lutz, C., and Lutz, P.G. (2019) The E3 ubiquitin ligase Asb2a in T helper 2 cells negatively regulates antitumor immunity in colorectal cancer. Cancer Immunology Research, 7:1332–1344.
Métais, A., Lamsoul, I., Melet, A., Uttenweiler-Joseph, S., Poincloux, R., Stefanovic, S., Valière, A., Gonzalez de Peredo, A., Stella, A., Burlet-Schiltz, O., Zaffran, S., Lutz, P.G.* and Moog-Lutz, C.* (2018) The Asb2α-Filamin A axis is essential for cytoskeletal remodeling during heart development. Circulation Research. 122: e34 (*: contributed equally to the work)
Spinner, C.A., Uttenweiler-Joseph, S., Métais, A., Stella, A., Burlet-Schiltz, O., Moog-Lutz, C. Lamsoul, I., and Lutz, P.G. (2015) Substrates of the ASB2α E3 ubiquitin ligase in dendritic cells. Scientific Reports, 5: 16269.
Lamsoul, I., Uttenweiler-Joseph, S., Moog-Lutz, C. and Lutz, P.G. Cullin 5-RING E3 ubiquitin Ligases, new therapeutic targets? Biochimie. pii: S0300-9084(15)00250-3. doi: 10.1016/j.biochi.
Zakaria, R., Lamsoul, I., Uttenweiler-Joseph, S., Erard, M., Monsarrat, B., Burlet-Schiltz, O., Moog-Lutz, C. and Lutz, P.G. (2013) Phosphorylation of serine 323 of ASB2α is pivotal for the targeting of filamin A to degradation, Cellular Signalling, 25: 2823-2830.
Lamsoul, I., Métais, A., Gouot, E., Heuzé, M.L., Lennon-Duménil, A.M., Moog-Lutz, C. and Lutz, P.G. (2013) ASB2α regulates migration of immature dendritic cells. Blood, 122: 533-541.
Uttenweiler-Joseph, S., Bouyssié, D., Calligaris, D., Lutz, P.G., Monsarrat, B. and Burlet-Schiltz, O. (2013) Quantitative proteomic analysis to decipher the differential apoptotic response of bortezomib-treated acute promyelocytic leukemia cells before and after retinoic acid-differentiation reveals an involvement of protein toxicity mechanisms. Proteomics, 13:37-47.
Lamsoul, I., Erard, M., van der Ven, P.F.M. and Lutz, P.G. (2012) Filamins but not Janus Kinases are substrates of the ASB2α Cullin-Ring E3 ubiquitin ligase in hematopoietic cells. PLoS ONE, 7: e43798.
Guiet, R., Verollet, C., Lamsoul, I., Cougoule, C., Poincloux, R., Labrousse, A., Calderwood, D.A., Glogauer, M., Lutz, P.G. and Maridonneau-Parini, I. (2012) Macrophage mesenchymal migration requires podosome stabilization by Filamin A. The Journal of Biological Chemistry. 287:13051-13062.
Lamsoul, I., Burande, C.F., Razinia, Z., Houles, T.C., Menoret, D., Baldassarre, M., Erard, M., Moog-Lutz, C., Calderwood, D.A., and Lutz, P.G. (2011) Functional and structural insights into ASB2α, a novel regulator of integrin-dependent adhesion of hematopoietic cells. The Journal of Biological Chemistry, 286: 30571-30581.
Razinia, Z., Baldassarre, M., Bouaouina, M., Lamsoul, I., Lutz, P.G. and Calderwood, D.A. (2011) The E3 ubiquitin ligase specificity subunit ASB2α targets filamins to proteasomal degradation by interacting with the filamin actin binding domain. Journal of Cell Science, 124: 2631-2642.
Baldassare, M., Razinia, Z., Burande, C.F., Lamsoul, I., Lutz, P.G., and Calderwood, D.A. (2009) Filamins regulate cell spreading and initiation of migration. PLoS ONE, 4(11):e7830.
Burande, C.F., Heuzé, M.L., Lamsoul, I., Monsarrat, B., Uttenweiler-Joseph, S., and Lutz, P.G. (2009) A label-free quantitative proteomic strategy to identify E3 ubiquitin ligase substrates targeted to proteasome degradation. Molecular & Cellular Proteomics, 8: 1719-1727.
Bello, N.F.*, Lamsoul, I.*, Heuzé, M.L., Métais, A., Moreaux, G., Duprez, D., Calderwood, D.A., Moog-Lutz, C., and Lutz P.G. (2009) The E3 ubiquitin ligase specificity subunit ASB2β is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation. Cell Death & Differentiation, 16: 921-932. *Contributed equally to the work.
Luissint, A.C., Lutz, P.G., Calderwood, D.A., Couraud, P.O., and Bourdoulous, S. (2008) JAM-L mediated leukocyte adhesion to endothelial cells is regulated in cis by α4β1 integrin activation. The Journal of Cell Biology, 183: 1159-1173.
Heuzé, M.L.*, Lamsoul, I.*, Baldassarre, M., Lad, Y., Lévêque, S., Razinia, Z., Moog-Lutz, C., Calderwood, D.A., and Lutz, P.G. (2008) ASB2 targets filamins A and B to proteasomal degradation. Blood, 112: 5130-5140. * Contributed equally to the work.
Heuzé, M. L., Lamsoul, I., Moog-Lutz, C. and Lutz, P. G. (2008). Ubiquitin-mediated proteasomal degradation in normal and malignant hematopoiesis. Blood Cells, Molecules & Diseases, 40: 200-210.
Denis, F.M., Benecke, A., Di Gioia, Y., Touw, I.P., Cayre, Y.E., and Lutz, P.G. (2005). PRAM-1 potentiates arsenic trioxide-induced JNK activation. The Journal of Biological Chemistry, 280: 9043-9048.
Heuzé, M.L., Guibal, F.C., Banks, C.A., Conaway, J.W., Conaway, R.C., Cayre, Y.E., Benecke, A., and Lutz, P.G. (2005). ASB2 is an elongin BC-interacting protein that can assemble with cullin 5 and rbx1 to reconstitute an E3 ubiquitin ligase complex. The Journal of Biological Chemistry, 280: 5468-5474.
Moog-Lutz, C., Cavé-Riant, F., Guibal, F.C., Breau, M.A., Di Gioia, Y., Couraud, P.O., Cayre, Y.E., Bourdoulous, S., and Lutz, P.G. (2003). JAML, a novel protein with characteristics of a Junctional Adhesion Molecule, is induced during differentiation of myeloid leukemia cells. Blood, 102: 3371-3378.
Rosa-Calatrava, M., Puvion-Dutilleul, F., Lutz, P., Dreyer, D., De Thé, H., Chatton, B., and Kedinger, C. (2003). Adenovirus protein IX sequesters host-cell promyelocytic leukaemia protein and contributes to efficient viral proliferation. EMBO Reports, 4: 969-975.
Lutz, P. G., Moog-Lutz, C., and Cayre, Y.E. (2002). Signaling revisited in acute promyelocytic leukemia. Leukemia, 16: 1933-1939.
Guibal, F.C., Moog-Lutz, C., Smolewski, P., Di Gioia, Y., Darzynkiewicz, Z., Lutz, P.G., and Cayre, Y.E. (2002). ASB-2 inhibits growth and promotes commitment in myeloid leukemia cells. The Journal of Biological Chemistry, 277: 218-224.
Esteve, L., Lutz, P., Thiriet, N., Revel, M-O., Aunis, D., and Zwiller, J. (2001). Cyclic GMP-dependent protein kinase potentiates serotonin-induced Egr-1 binding activity in PC12 cells. Cellular Signaling, 13: 425-432.
Moog-Lutz, C.*, Peterson, E.J.*, Lutz, P.G.*, Eliason, S., Cavé-Riant, F., Singer, A., Di Gioia, Y., Dmowski, S., Kamens, J., Cayre, Y.E., and Koretzky, G. (2001). PRAM-1 is a novel adaptor protein regulated by retinoic acid (RA) and promyelocytic leukemia (PML)-RA receptor α in acute promyelocytic leukemia cells. The Journal of Biological Chemistry 276: 22375-22381. * Contributed equally to the work.
Lutz, P.G., Houzel-Charavel, A., Moog-Lutz, C., and Cayre, Y.E. (2001). Myeloblastin is a Myb target gene; mechanisms of regulation by retinoic acid in myeloid leukemia cells. Blood 97:2449-2456.
Lutz, P.G., Moog-Lutz, C., Coumau-Gatbois, E., Kobari, L., Di Gioia, Y., and Cayre Y.E. (2000). Myeloblastin is a granulocyte colony-stimulating factor responsive gene conferring factor-independent growth to hematopoietic cells. Proceedings of the National Academy of Sciences, USA. 15: 1601-1606.
Lutz, P., Rosa-Calatrava, M., and Kedinger, C. (1997). The product of the adenovirus intermediate gene IX is a transcriptional activator. Journal of Virology 71:5102-5109.
Gustin, K., Lutz, P., and Imperiale, M.J. (1996). Interaction of the adenovirus L1 52/55-kilodalton protein with the IVa2 gene product during infection. Journal of Virology 70:6463-6467.
Lutz P., Puvion-Dutilleul, F., Lutz,Y., and Kedinger, C. (1996). Nucleoplasmic and nucleolar distribution of the adenovirus IVa2 gene product. Journal of Virology 70:3449-3460.
Lutz, P., and Kedinger, C. (1996). Properties of the adenovirus IVa2 gene product, an effector of late-phase-dependent activation of the major late promoter. Journal of Virology 70:1396-1405.
Tribouley, C., Lutz P., Staub, A. and Kedinger, C. (1994). The product of the adenovirus intermediate gene IVa2 is a transcriptional activator of the major late promoter. Journal of Virology 68:4450-4457.
Scientific summary
A tight regulation of lymphocyte differentiation and activation is of uttermost importance to set calibrated adaptive immune responses. This is largely achieved through transcriptional and epigenetic regulations. While powerful, these mechanisms do not allow cells to acutely adapt or fine‐tune cellular processes. For this purpose, post-translational modifications such as ubiquitylation – the conjugation of ubiquitin to a protein substrate – are used. Ubiquitylation is rapid, reversible and versatile, directing proteins to proteasomal degradation and additional fates. The reversibility of this post-translational modification is driven by deubiquitinating enzymes responsible for removing ubiquitin conjugates from substrates. Importantly, alteration of the ubiquitin pathway results in human disease pathogenesis including cancer and leukemia, neurological disorders or inflammatory and infectious diseases. In this context, we focus on ubiquitin enzymes regulating the precise dosage or activity of signaling hubs and actin cytoskeletal proteins that play key roles in immune cells. The overall goal of our project is to better understand ubiquitylation/deubiquitylation events in immunity and disease in order to identify novel biomarkers and therapeutic targets for precision medicine.
A key regulatory step of the ubiquitylation cascade is governed by the E3 ubiquitin ligase, which dictates substrate selectivity. Several E3 ubiquitin ligases regulate T cell differentiation and functions. We have recently gathered solid molecular, cellular and in vivo evidence that the ASB2α E3 ubiquitin ligase controls T helper 2 lymphocyte functions in a mouse model of colon cancer. ASB2α triggers ubiquitylation (K48-linked polyubiquitin chains) and proteasomal degradation of the actin-binding proteins filamin A and filamin B, thereby regulating actin cytoskeleton organization and remodeling, as well as different aspects of cell motility. One of our specific goals is therefore to elucidate the roles of the ASB2α E3 ubiquitin ligase in the regulation of lymphocyte function in physiological and pathological settings.
