Dissecting the signalling cascade in the vertebrate spindle assembly checkpoint

Projektinformationen

KINETOCHECK

ID Finanzhilfevereinbarung: 500490

Startdatum 1 März 2004

Enddatum 28 Februar 2006

Finanziert unter

• Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006

Gesamtkosten € 214 590,00

EU-Beitrag € 214 590,00

Koordiniert durch

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France

Ziel

The mitotic checkpoint acts to inhibit entry into anaphase until all chromosomes havesuccessfully attached to spindle microtubules. Unattached kinetochores are believed to release inactivated form of proteins such as BubR1 and Mad2 that inhibits APC/C-dependent ubiquitinylation and subsequent proteolysis of components needed for anaphase onset.
Previous work by Dr. Abrieu(the host laboratory) has shown that the kinase Mps1 is required to recruit some checkpoint components onto the kinetochore, including CENP-E, a kinesin-like protein acting as a sensor of kinetochore to microtubules attachment. My work in this lab will consist on further dissecting the regulation of CENP-E by Mps1 in this context, using biochemical, chimiogenetic and microspectroscopic approaches. This will involve developing a new method to identify Mps1substrates; a multidisciplinary approach (chimiogenetic) in tight collaboration with the organic chemistry laboratory of Prof. Perigaud. I am also proposing to identify the minimal kinetochore binding domain of CENP-E. This will allow me to follow its activation, and regulation of the downstream kinaseBubR1 at the kinetochore by FRET (Fluorescence Resonance Energy Transfer). Finally, I will try to uncover new kinetochore proteins by fishing for binding partners of two outermost kinetochore components (CENP-E and Mps1) and the innermost centromeric protein (CENP-A). Altogether, this proposal should provide a better understanding of the checkpoint regulation at the kinetochore, a process whose deregulation is leading to aneuploidy, a hallmark of cancer.
Hopefully, these studies could lead to new therapeutic development specifically targeting cancer cells by directly activating checkpoint regulators, thus preventing side effects onto normal cells.

Wissenschaftliches Gebiet

• Agrarwissenschaften › Landwirtschaft, Forstwirtschaft und Fischerei › Fischerei
• Naturwissenschaften › Chemiewissenschaften › organische Chemie
• Naturwissenschaften › Biowissenschaften › Biochemie › Biomoleküle › Proteine
• Medizin- und Gesundheitswissenschaften › Klinische Medizin › Onkologie
• Naturwissenschaften › Biowissenschaften › Genetik › Chromosom

Schlüsselbegriffe

• Cell cycle
• Kinase
• Kinetochore
• Mitotic checkpoint
• Molecular Motor

Programm/Programme

• FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006

Thema/Themen

• MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF)

Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-5
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

EIF - Marie Curie actions-Intra-European Fellowships

Koordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

• Adresse: Rue michel ange 3 ; Paris ; Frankreich
• EU-Beitrag: Keine Daten