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Contenuto archiviato il 2024-05-29

A novel mitotic signalling pathway composed by the NIMA family protein kinases Nercc1, Nek6 and Nek7. Regulation, functions, and possible implication in cellular transformation

Obiettivo

It is proposed to study a novel mammalian signalling pathway composed of the NIMA-family protein kinases Nercc1/Nek9, Nek6 and Nek7. Neks are related to NIMA, an Aspergillus kinase required for mitotic entry, and are involved in chromatin condensation and formation of the spindle. Nercc1 was identified as a human Nek that binds, phosphorylates and activates two members of the same family, the homologous Nek6 and Nek7.

Nercc1 is active at the centrosomes and spindle poles during mitosis, and interference with the kinase function results in spindle abnormalities and incorrect chromosome alignment, resulting in prometaphase arrest or abnormal chromosome segregation and aneuploidy. It is proposed to study the regulation of the Nercc1/Nek6/7 signalling cassette, as well as to identify substrates of these kinases and determine their role during mitosis and the formation of the spindle. I will seek to determine the mechanism that keeps Nercc1 inactive in interphase and activates it in mitosis, as well as to identify Nercc1 and Nek6/7 binding partners.

The role of the kinases during mitosis will be studied through the use of different inhibiting strategies, including the production of knockout cells and mice. The goal of this proposal is to understand the position of the Nercc1/Nek6/7 pathway in the midst of different signalling pathways that control and execute mitosis, to determine whether its deregulation may be involved in cellular transformation through contribution to genetic instability, and to identify Nercc1 inhibitors and assess them as therapeutic anti-mitotic drugs.

Campo scientifico (EuroSciVoc)

Parole chiave

Argomento(i)

Invito a presentare proposte

FP6-2004-MOBILITY-12
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Meccanismo di finanziamento

IRG - Marie Curie actions-International re-integration grants

Coordinatore

INSTITUT DE RECERCA BIOMEDICA DEL PARC CIENTIFIC DE BARCELONA
Contributo UE
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Costo totale
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