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Analysis of the alternatively spliced isoforms of human intersectin 1 and 2: characterization of their expression patterns in normal and tumour tissues

Objective

Intersectins are a highly conserved family of proteins that work as key regulators of both endocytosis and intracellular signalling pathways. Being multimodular proteins, they participate in a network of interactions that are relevant for the cell homeostasis. Preliminary work from some of the participant teams in this proposal has revealed that intersectin genes can generate, through alternative splicing, many protein isoforms with different domain composition.

We hypothesize that changes in the domain composition of the intersectin proteins may influence on their interaction with other partners, and therefore on their function. To address this hypothesis, we propose to analyze the products of alternative splicing events for intersectin 1 and 2 (human and mouse) both at the RNA and protein levels. This will require the generation of valuable tools such as specific antibodies to the different protein domains of intersectins. The expression patterns of the spliced isoforms will be compared in normal and tumour tissues.

In addition, the binding activity of the different intersectin isoforms towards known interactors will be assessed to find out how changes in the domain composition in intersectins affect their relationship with their functional partners. We expect that the combination of the information obtained from the expression profiles in tumour samples together with the binding properties identified for the splicing-derived isoforms will allow us to get some insights in intersectin roles during tumour development.

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Coordinator

CENTER FOR GENOMIC REGULATION (CRG)

Address

Passeig Maritim, 37-49
Barcelona

Spain

Administrative Contact

Susana DE LA LUNA

Participants (3)

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INSTITUTE OF MOLECULAR BIOLOGY AND GENETICS OF NASU

Ukraine

KAROLINSKA INSTITUTE

Sweden

PALLADIN INSTITUTE OF BIOCHEMISTRY

Ukraine

Project information

Grant agreement ID: INTAS 2005-1000004-7762

  • Start date

    1 June 2006

  • End date

    31 May 2008

Funded under:

IC-INTAS

  • Overall budget:

    € 99 350

  • EU contribution

    € 150 000

Coordinated by:

CENTER FOR GENOMIC REGULATION (CRG)

Spain