Objective
The binding of TGF-b to its receptors induces phosphorylation of Smad2 and Smad3, their subsequent association to Smad4 and their nuclear translocation. In the nucleus, the Smad3/Smad4 and Smad2/Smad4 heterodimers act as transcription factors and induce specific target genes. TGF-b pathway has a tumor suppressor function characterized by its ability to inhibit cell growth. Many cancer cell lines have acquired resistance to the antiproliferative effect of TGF-b. This is mainly achieved through loss of function mutations or deletions that affect TGF-b receptors or Smad4, particularly in colon cancer and pancreatic cancer. During my Postdoctoral training in Caroline Hill’s laboratory, I have shown that the E3 Ub-ligase Arkadia is involved in the degradation of the transcriptional repressor SnoN and is therefore absolutely required for the activation of Smad3/Smad4 target genes such as PAI-1. The laboratory of Azeddine Atfi has recently performed a two-hybrid screen using another repressor of the pathway, TGIF, as a bait. This study has led to the identification of a new partner of TGIF, TIP11 (TGIF interacting protein 11), which is a new potential E3 Ub-ligase. Preliminary results indicate that TIP11 also contributes to TGF-b responses. Recently, we both have independently identified that Arkadia and TIP11 can be altered in tumor cell lines. Our study aimed to determine whether these two E3 Ub-ligases, essential for the TGF-b pathway, are novel tumor suppressor genes. Our objectives are: (1) to identify Alterations of Arkadia and TIP11 in human carcinoma cell lines and tumor samples. (2) to study the function of Arkadia and TIP11 by reintroducing Arkadia or TIP11 in deficient cell lines, in order to better understand their role in TGF-b signaling and tumorigenesis. (3) to unravel the mechanism of action of these two E3 Ub-ligases by a biochemistry approach. (4) to identify novel binding partners of Arkadia and TIP11 by performing a two-hybrid screen.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology colorectal cancer
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology pancreatic cancer
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2007-2-2-ERG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
75654 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.