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Regulation of the Tumor Suppressor LKB1 by the Acetyltransferase GCN5 Maya Ghawitian

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Regulation of the Tumor Suppressor LKB1 by the Acetyltransferase GCN5 Maya Ghawitian Regulation of the tumor suppressor LKB1 by the acetyltransferase GCN5 Maya Ghawitian To cite this version: Maya Ghawitian. Regulation of the tumor suppressor LKB1 by the acetyltransferase GCN5. Cancer. Université Grenoble Alpes, 2015. English. NNT : 2015GREAV039. tel-01514167 HAL Id: tel-01514167 https://tel.archives-ouvertes.fr/tel-01514167 Submitted on 25 Apr 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THESIS To obtain the degree of DOCTOR FROM UNIVERSITY OF GRENOBLE ALPES Specialty: Cellular biology Ministerial order: August 7, 2006 Presented by « Maya GHAWITIAN» PhD thesis supervised by « Jean VIALLET » and co-supervised by « Marc BILLAUD » Prepared in team 3 of the Albert Bonniot Institute at the Ecole Doctorale Chimie et Sciences du Vivant Regulation of the tumor suppressor LKB1 by the acetyltransferase GCN5 Defended in public « June 18, 2015 », In front of the jury composed of: Mrs. Christine PERRET DR1 (INSERM) Cochin Institute INSERM U1016 - CNRS UMR8104 - Paris Descartes University (President) Mr. Benoit VIOLLET DR2 (INSERM) Cochin Institute INSERM U1016 - CNRS UMR8104 - Paris Descartes University (Reviewer) Mr. Guy MOUCHIROUD DR1 (INSERM) CG(phi)MC UMR 5534, Lyon 1 University (Reviewer) Mr. Saadi KHOCHBIN DRCE (CNRS) Albert Bonniot Institute CRI INSERM/UJF U823, Grenoble/La Tronche (Examiner) Mr. Jean VIALLET MCU (UJF) Albert Bonniot Institute CRI INSERM/UJF U823, Grenoble/La Tronche (Supervisor) Mr. Marc BILLAUD DR1 (CNRS) Albert Bonniot Institute CRI INSERM/UJF U823, Grenoble/La Tronche (Co-supervisor) THÈSE Pour obtenir le grade de DOCTEUR DE L’UNIVERSITÉ GRENOBLE ALPES Spécialité: Biologie cellulaire Arrêté ministériel : 7 août 2006 Présentée par « Maya GHAWITIAN» Thèse dirigée par « Jean VIALLET » et co-dirigée par « Marc BILLAUD » Préparée au sein de l´équipe 3 de l´Institut Albert Bonniot à l'École Doctorale Chimie et Sciences du Vivant Régulation du suppresseur de tumeur LKB1 par l´acétyltransférase GCN5 Thèse soutenue publiquement le « 18 juin 2015 », devant le jury composé de : Mme Christine PERRET DR1 (INSERM) Institut Cochin INSERM U1016 - CNRS UMR8104 – Université Paris Descartes (Présidente) Mr. Benoit VIOLLET DR2 (INSERM) Institut Cochin INSERM U1016 - CNRS UMR8104 – Université Paris Descartes University (Rapporteur) Mr. Guy MOUCHIROUD DR1 (INSERM) CG(phi)MC UMR 5534, Université Lyon 1 (Rapporteur) Mr. Saadi KHOCHBIN DRCE (CNRS) Institut Albert Bonniot CRI INSERM/UJF U823, Grenoble/La Tronche (Examinateur) Mr. Jean VIALLET MCU (UJF) Institut Albert Bonniot CRI INSERM/UJF U823, Grenoble/La Tronche (Directeur de thèse) Mr. Marc BILLAUD DR1 (CNRS) Institut Albert Bonniot CRI INSERM/UJF U823, Grenoble/La Tronche (Co- directeur de thèse) “Important thing in science is not so much to obtain new facts as to discover new ways of thinking about them” (Sir William Bragg) “The secret of life, though, is to fall seven times and to get up eight times.” (Paulo Coelho) ”The roots of education are bitter, but the fruit is sweet.” (Aristotle) Acknowledgements It is time for me to embark on a new adventure, and the past years, especially the ones I spent working on my PhD, have armed me with enough knowledge, strength and patience to embrace my future path. This PhD was for me a scientific but also a personal experience that made me grow in different ways. Therefore, I would like to thank all the people who´ve crossed my path, and maybe without knowing it, have contributed to making me the person I am today. First, I would like to thank the members of the jury, namely: Mrs. Christine Perret, Mr. Benoit Viollet and Mr. Guy Mouchiroud, for kindly accepting to evaluate my thesis, as well as for your comprehension and patience when needed for the organization of my PhD defense. Mr. Saadi Khochbin, special thanks, not only for accepting to be part of this jury, but also for your tireless availability, support and kindness as well as for all the enriching scientific discussions and advices you gave me throughout my PhD. Jean Viallet, for initiating me, supporting me and giving me the opportunity to develop my teaching experience at the university. Last but not least, I would like to thank Marc Billaud, for welcoming me in the new team that he was founding in Grenoble, a team with which I´ve also progressed. Thank you Marc for your support, your advices, the opportunities that you gave me, for the time you spent with me on grants applications and for accompanying me at the end of this PhD in order to get the best of it. I hope that today, when you see the road I´ve travelled, you´re proud of what I´ve learned and the person I´ve become. You´re an admirable scientist and I wish you the best for your future projects. I also thank our collaborators and members of my thesis committee, namely: Mrs. Sophie Creuzet, for your advices and encouragements. It was an honor for me to have a scientific collaboration with you. Mr. Vincent Mirouse, for our discussions during the advisory PhD commitees and for kindly providing us with your home-made antibody, the main tool that allowed me to conduct my project. I also thank the ARC (association pour la recherche sur le cancer) and FRM (foundation pour la recherche médicale) associations for funding my third and fourth years of PhD respectively. Special thanks to the members of our team: Thank you Sakinou, for welcoming me when I first arrived in this team, for always taking care of my nutrition and well-being, and especially for your delicious home-made “cornes de gazelle”. Thank you for opening up your heart to me and for giving me rides to the train station at 4 a.m! You´re so giving and caring and I advise no one to get on your “nerves”… Thank you Chantalou, or should I say “TAAZ”, for your extraordinarily tireless dynamism, for our mutually enriching scientific afternoon discussions, for your collaboration on the GCN5 project and of course your daily smile. You´re a model for hard work and ambition! My dear sweet Anca… there´s a bright future for you out there…hopefully Coca (cola)-free! Thank you for being the freshness of the team, for your hard work and your smile. You´re a beautiful person inside and out. Sandrine, thanks for your help and your pleasant presence. You´ve learned a lot in a short time, always with pleasure, enthusiasm and curiosity. Make good use of the small “tricks” (tin, tin, tin)! Chloé, I will always remember shooting that famous “scene” with Anne, my ribs still hurt from laughing. I wish you good luck with your PhD, and cross my fingers for your future publication. Laurence, thank you for your daily communicative good mood. You´re a remarkable person, a model of courage, leadership and scientific success for all women. Jacques, “Mr. in situ”, the team´s painter, a multi-talented researcher… Clotilde, I will remember the happy moments we shared in the lab. Thanks to the former members of the team: Nico, the perfect devotion as a father and as a scientist. Audrey, “the free electron” and “zen-attitude mistress”. Caroline, the strawberry milkshake culture medium specialist. Renaud, our chemistry genius. Nouna, our sunshine and microscopy expert, thanks for the Friday evening craziness, your humor and our “fexe” discussions. My dear Véro, thanks for your trust, your support, your kindness and for never failing me. I will always admire your courage and the devoted mother you are. Emilien, alias “Milou”, thanks for being my bench-mate, for your humor, your “boeuf” attitude and our weekly “game of thrones” debates. I also thank the friendly and pleasant trainees Déborah, Aurélia, Dimi, Christopher and Sylvain for passing-by bringing freshness and renewal to our team, as well as Bruno who spent a few months in our team as a collaborator, it was a pleasure meeting you and debating over some LKB1 mysteries with you after long working days. Thanks to the members of team 1: Our sister-team…It was a pleasure to greet you all every morning, to work next to your lab, and very often in your lab… Special thanks: To Sandra, you´re a sunshine, kind, caring and helpful. To Christiane, thanks for being my molecular biology teacher! To Ingrid, thanks for your kindness and for letting me use your benchtop pump for my numerous IPs! To Christos, my PhD mate. To my dear Sanela, although it was for a short time, I was extremely happy and lucky to meet you. Your overflowing motivation is inspirational. Thanks for being of great support. To my dear Sacho, thanks for being there, for being so helpful in every way without expecting anything in return…but BEERS!!! Ok, THAT WAS EASY! Thanks for being so crazy and so funny. You ROCK! Thanks to Christian Villiers and the administrative staff without whom we could not work… Charlotte, Aude, Céline, Grégory, Natacha and Dalenda, thanks for your daily help and for always doing your best to find suitable solutions. And thanks Johanna for your cheerful attitude. It was great working with you all. …and the technical staff as well, namely: Michail, Benjamin, Norbert and Liliane. Thanks to all the persons from the other teams with whom I´ve interacted: Team 6, and more particularly Karin, “vielen Dank” for all our scientific debates and your suggestions.
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