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Wednesday 14 April 2004

protein farnesylation, farnesylation


Definition: Prenylation consists of the addition of an isoprenoid group to a cysteine residue located near the carboxyl terminal of a protein, or the addition of hydrophobic molecules to a protein or chemical compound.

It is usually assumed that prenyl groups (3-methyl-but-2-en-1-yl) facilitate attachment to cell membranes, similar to lipid anchors like the GPI anchor, though direct evidence is missing.

Prenyl groups have been shown to be important for protein–protein binding through specialized prenyl-binding domains.

This enzymatic post-translational modification is important for the maturation and processing of proteins.

Both processes are necessary to mediate protein-protein and membrane-protein associations, in addition to regulating the localisation and function of proteins.

The severe phenotype of animals deficient in enzymes involved in both prenylation and maturation highlights the significance of these processes.

Moreover, alterations in the genes coding for isoprenylated proteins or enzymes that are involved in both prenylation and maturation processes have been found to be the basis of severe human diseases, such as cancer, neurodegenerative disorders, retinitis pigmentosa, and premature ageing syndromes.

Recent studies on isoprenylation and postprenylation processing in pathological conditions have unveiled surprising aspects of these modifications and their roles in different cellular pathways.

The identification of these enzymes as therapeutic targets has led researchers to validate their effects in vitro and in vivo as antitumour or antiageing agents.

See also

- farnesyl transferase
- farnesyl transferase inhibitors (FTIs)


- FTIs are signal transduction inhibitors that display promising clinical activity against a broad spectrum of malignancies.


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