Radiation induced signalling cell cycle control

Información del proyecto

Identificador del acuerdo de subvención: FI4P960052

Proyecto cerrado

Fecha de inicio 1 Enero 1997

Fecha de finalización 30 Junio 1999

Financiado con arreglo a

• Specific research and training programme in the field of nuclear safety and safeguards, 1994-1998

Coste total

Sin datos

Aportación de la UE

Sin datos

Coordinado por

Rijksuniversiteit Leiden
Netherlands

Objetivo

This research proposal focuses on various aspects of the response of mammalian cells to ionizing radiation. The purpose will be to gain a better understanding of how radiation triggers signalling cascades and how these cascades culminate in cell-cycle control, and, at a later stage, may lead to such diverse phenomena as programmed cell death (apoptosis), initiation of oncogenic transformation and effects on the immune system. This proposal will address the mode of activation as well as the possible role of several intermediates of these ionizing radiation-induced signalling responses. In addition, it will be attempted to identify novel genes that are responsive to ionizing radiation and constituents of these signalling routes.
Firstly, this proposal concerns the activation by ionizing radiation of the transcription factors NFkB, KBFl and cJun/ATF2. These transcription factors are crucial targets of two well-known radiationactivated signal transduction pathways. Secondly, the radiationinduced stabilization of the transcription factor p53, a key component in activation of cell-cycle arrest and programmed cell death (apoptosis), will be investigated. Thirdly, ionizing radiation of mammalian cells seems to activate responses that lead not only to apoptosis but also to cellular protection. We want to get insight into these relatively unknown protective responses. In this respect we will study the activation and role of c-Fos and ornithine decarboxylase (ODC) upon ionizing radiation as depletion of any of these two proteins renders cells highly sensitive to radiation. Interestingly, both genes have been characterized as proto-oncogenes and play important roles at the Gl stage of the cell cycle. Fourthly, we will isolate human genes which are specifically activated by ionizing radiation via a signal transduction route which is probably independent of p53 and not shared by other DNA damaging agents. Similarly, we will isolate genes which are induced by ionizing radiation in a p53-dependent manner in tissues which will readily go into apoptosis. The identification of these genes and the analysis of their expression in normal and tumour tissue and in the tissues of individuals exposed to genotoxic agents has the potential to provide immense insight into the function of p53 and may identify many new genes of importance in human cancer.

Ámbito científico (EuroSciVoc)

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Programa(s)

• EAEC-NFS 2 - Specific research and training programme in the field of nuclear safety and safeguards, 1994-1998

Tema(s)

• 040102 - Repair of, and recovery from, DNA damage and radiation sensitivity

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

CSC - Cost-sharing contracts

Coordinador

Rijksuniversiteit Leiden

• Aportación de la UE: Sin datos
• Dirección: 72,Wassenaarseweg ; 2300 AL Leiden ; Países Bajos
• Coste total: Sin datos

Participantes (2)

Forschungszentrum Karlsruhe GmbH - Technik und Umwelt

Alemania

• Aportación de la UE: Sin datos
• Dirección: 5, ; 76344 Karlsruhe
• Coste total: Sin datos

UNIVERSITY OF DUNDEE

Reino Unido

• Aportación de la UE: Sin datos
• Dirección: DD1 9SY DUNDEE
• Coste total: Sin datos