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Smad4-Ubiquitination by opposing E3 and DUB activities: a central control element in TGF-beta signaling

Smad4-Ubiquitination by opposing E3 and DUB activities: a central control element in TGF-beta signaling

Objective

The research here outlined deals with the relevance of ubiquitination in TGF-beta growth factor signalling. As outlined below (subchapters) TGF-beta signalling is fundamental for embryonic development and for a variety of human pathologies. In particular, recent data showed that tuning TGF-beta signalling is essential for differentiation of pluripotent cells and for cancer and metastasis. The proposal is therefore highly relevant not only scientifically but also for the socio-economic reasons. We will place emphasis of monoubiquitination as a mechanism to regulate protein function, which is a new concept emerging in signal transduction. Multidisiplinarity. As TGF-beta is such a pleiotropic cytokine, the research is highly multidisciplinary, ranging from biochemistry of the Smad4 signal transducer, to identification of new enzymes impinging on Smad4 ubiquitination levels, and how these events ultimately impact on the embryonic development and proliferative behaviour of adult cells. The reason for me to apply to this incoming international fellowship is to linked my specific expertise, that is, the ability to carry out special type of manipulations such as depletion of maternal mRNA in Xenopus oocytes (that are simply not present in Europe) or generation of transgenic frogs (poorly diffused). These technologies will be of help to the characterization of the embryonic phenotype of Smad4 modifying enzymes that are supplied maternally to the conceptus. Being the hosting laboratory a world leader in the TGF-beta signalling and embryonic development field, these expertise will now be able to spread in Europe. My own expertise will therefore integrate with those of the hosting group leading to a mutually beneficial and synergistic approach to a very complex and daring biological problem.
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Coordinator

UNIVERSITA DEGLI STUDI DI PADOVA

Address

Via 8 Febbraio 2
35122 Padova

Italy

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 162 985,98

Administrative Contact

Stefano Piccolo (Prof.)

Project information

Grant agreement ID: 221008

Status

Closed project

  • Start date

    1 February 2009

  • End date

    31 January 2011

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 162 985,98

  • EU contribution

    € 162 985,98

Coordinated by:

UNIVERSITA DEGLI STUDI DI PADOVA

Italy