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The AAA ATPase p97: from the use of genetics to the development of new chemical tools to study its functions

Defense Thèse de doctorat : Univ. Genève, 2018 - Sc. 5173 - 2018/01/23
Abstract p97/CDC-48 is an AAA+ ATPase involved in many functions along the cell cycle. p97 was discovered for its involvement in cell division, but its underlying mechanisms during mitosis are not well understood yet because its depletion cause aberrant phenotypes which complicate the analysis of its functions. To overcome this problem, researchers have been studying its adaptor proteins to uncover new p97 functions and its mechanisms. Another method to study p97 functions consists in using p97 inhibitors to have temporal resolution. The available p97 inhibitors are very efficient and potent in inhibiting p97 and usually cells undergo apoptosis upon treatment with these drugs. To study p97 functions in this thesis, we used in one side genetic tools, to study the role of UBXN-2 , a p97 adaptor, in regulating spindle orientation in the one-cell embryo of C. elegans, and on the other side, we isolated new chemical tools that affect p97 function by performing two screens with different objectives. Our data provide a new regulation mode of UBXN-2 in regulating spindle orientation in mitosis. In addition, we present new chemical tools that will help the p97 field to better understand the mechanisms governing its functions and, maybe, uncover new roles yet unknown.
Keywords P97AAA+ ATPaseCell divisionInhibitorsAllosteric modulators
URN: urn:nbn:ch:unige-1025134
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FIGUEROLA CONCHAS, Ainoa. The AAA ATPase p97: from the use of genetics to the development of new chemical tools to study its functions. Université de Genève. Thèse, 2018. doi: 10.13097/archive-ouverte/unige:102513 https://archive-ouverte.unige.ch/unige:102513

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Deposited on : 2018-02-23

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