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Enzymes: Structure and activity

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  1. Intoduction
  2. PART I: The Kyoto Protocol
    1. Global warming
    2. The vertices of the earth
    3. The contents of the Protocol
  3. PART II: American diplomacy around the Kyoto Protocol
    1. General Remarks
    2. The positions of the presidents of the United States before the Kyoto Protocol
    3. The presidencies of Bill Clinton (1993-2001)
    4. The term of George W. Bush (2001-2009)
  4. Conclusion

Article: Human carcinoma cell growth and invasiveness is impaired by the propeptide of the universal proprotein convertase furin. Authors: Ricardo Lopez de Cicco, Daniel E. Bassi, Stanley Zucker, Nabil G. Seidah and P. Andres J. Klein-Szanto.

The role of a proprotein convertase is to transform a substrate inactive to its active form. To date, nine proprotein have been discovered in mammals. Furin, a proprotein convertase, is secreted at a physiological level in all body cells. If it is over secreted it, among other things, activates many substrates that are characteristic to the development of a cancer. These characteristics are metalloproteinases, growth factors, receptors for growth factors and adhesion molecules.

Furin is synthesized as an inactive enzymatic precursor in order to avoid a premature proteolytic reaction. This inhibitory mechanism depends on the presence of a preprosegment inactivator of furin, graded as ppFur at the NH2 terminus of the precursor. As long as it remained at the proprotein, it had no activity on its substrates.

After autocatalytic cleavage in the endoplasmic reticulum where ppFur remains with the precursor, ppFur dissociates in the Golgi and thus, the proprotein becomes active. Furin will then activate other substrates including MT1-MMP (membrane type 1 matrix metalloproteinase), TGF- ? (transforming growth factor- ?), IGF-2 (insulin-like growth factor-2), the IGF-1R (insulin-like growth factor-1 receptor) and VEGF-C (vascular endothelial growth factor-C).

In the ongoing fight against cancer, the authors transfected ppFur to cancer cell lines. They observed the effects on the substrates of furin. Their goal was to see whether cell proliferation, invasive potential, tumorigenicity and the power of the angiogenic tumor was reduced.

Colony formation in soft agar:
There is evidence that a link exists between the ability of a cell to form a colony in soft agar and its transformation into a cancer cell. The authors wanted to know if, transfecting cell lines with ppFur would reduce the number of colonies.
With an illustration they show us that all cell lines transfected with ppFur carry fewer colonies and that the rate is specific to each lineage.
This tells us that ppFur has a negative role in the formation of colonies.

The effects of furin preprosegment on the invasiveness of cell lines of squamous cell carcinoma of the head and neck:
One important characteristic of cancer cells is their ability to spread in the body. This feature can be evaluated by its invasive potential. The authors have estimated this by counting the number of transfected cells that degrade and pass through a Matrigel coat. The experiment was performed in vitro.
With another illustration the authors show us that ppFur inhibits the invasive potential of cells.

The effects of furin preprosegment on the tumorigenicity of cell lines of the squamous cell carcinoma of the head and neck:
The Tumorigenicity is judged by statistics. SCID mice were used for testing (that is to say that they were neither T cells nor B cells)

The test analysis of variance (ANOVA: Analysis Of Variance) and the log-rank test shows that there is a significant difference between the rate of growth of cells transfected with VA and that of cells transfected with ppFur.

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