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Activity Report IFOM 2005

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Complete list of IFOM Publications 2005

In 2005 the IFOM scientists published 90 research articles in international scientific magazines, with an average impact factor of 9.2227.

The transferrin receptor
Metabolism and cancer
Dangerous chromosomal structures
Regulation of cellular division

The transferrin receptor

Amongst the articles published in 2005 we wish to highlight an article published in December in the Cell magazine:

"TTP specifically regulates the internalization of the transferrin receptor" (Tosoni et al. Cell 2005; PMID: 16325581 impact factor 28.3890).

report An IFOM Researcher

Scientists have discovered that a molecule, the TTP (Transferrin receptor Trafficking Protein) has a specific role in regulating the endocytosis mechanism of the transferrin receptor.
In addition to its importance in terms of discovering cell mechanisms, this discovery is particularly significant on account of the fact that in many tumours, an overabundance of transferrin receptors, has been detected - the tumour cells have high metabolism and therefore need much iron.
The TTP, which is able to inhibit receptor mediated endocytosis, could act as a potential onco-suppressor. It remains to be tested whether the TTP can be used as a possible therapeutic target.

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Metabolism and cancer

An essential step forward in cancer research has been taken thanks to the study:

"Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis" (Giorgio et al., Cell; PMID: 16051147 impact factor 28.3890), published in July in the Cell magazine.

report Researcher at the IFOM laboratories

The results of this research project contribute to clarifying, in molecular terms, the correlation between cell metabolism mechanisms and cancer. In cells, the "respiration" function (that is the production of energy from oxygen and glucose) is carried out by the mitochondria. Scientists have discovered the molecular mechanism whereby a protein, p66, produces, both in normal cells and in pathological cells, free radicals (ROS), which, in turn, are responsible for causing alterations at a mitochondrial level. As it is well known that a) in neoplastic cells there is an increase in free radicals and b) the same cells have a low level of mitochondrial activity, studies carried out by Marco Giorgio and his colleagues finally place the two phenomena in a clear cause and effect relationship. Thereby contributing to narrow the focus down to those mechanisms which, in the event of malfunctioning, may alter the primary processes of cell life and induce neoplastic degeneration. Here too the final objective is to identify the therapeutic target to strike in order to attempt to restore normal cellular functions in the neoplastic cells.

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Dangerous chromosomal structures

Another potential therapeutic target in the battle against cancer has been highlighted in the study:

"Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase", (Liberi et al., Genes Dev 2005; PMID: 15687257 impact factor 16.3850), appearing in the February edition of the magazine Genes Development.

report Saccharomyces cerevisiae yeast

Using the Saccharomyces cerevisiae yeast as a model organism, the researches succeeded in discovering the cause of the genetic instability which can be observed in some syndromes, especially in Bloom's syndrome (a rare illness which recapitulates the symptomology and the molecular defects of many tumours). Giordano Liberi and his colleagues discovered that a specific mechanism actively generates dangerous chromosomal structures in sick cells: this mechanism, which acts in many tumours, could therefore represent a possible target against which pharmacological weapons could be aimed.

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Regulation of cellular division

Finally, the study:

"Mechanism of Aurora B activation by INCENP and inhibition by Hesperadin" (Sessa et al., Mol. Cell 2005; PMID: 15866179 impact factor 16.8110) published in April in the Molecular Cell magazine,

shows the three dimensional structure, obtained with crystallography techniques, of the Aurora B protein and describes the activation mechanism on the part of its interactor, the INCEP protein). Aurora B belongs to the Aurora kinase family, which plays a crucial role in regulating cell division and especially mitosis. In various tumours irregular Aurora A and B activity has been found. For this reason these kinases represent potential therapeutic targets. The structural and functional characterisation of Aurora B therefore represents an important step forward in the molecular cancer research.

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