protein farnesylation

Definition

Target type: biologicalprocess

The covalent attachment of a farnesyl group to a protein. [GOC:jl]

Protein farnesylation is a post-translational modification crucial for the localization, stability, and function of a diverse set of proteins, primarily involved in signaling pathways and membrane interactions. This process involves the covalent attachment of a 15-carbon isoprenoid lipid called farnesyl to a cysteine residue near the C-terminus of the target protein. The farnesyl group is derived from the mevalonate pathway, a metabolic route that produces essential isoprenoids. Farnesylation is catalyzed by a family of enzymes known as protein farnesyltransferases (FTases), which are heterodimers composed of an alpha and a beta subunit. The FTase recognizes a specific sequence motif near the C-terminus of the target protein, typically a cysteine residue followed by two aliphatic amino acids (often alanine or methionine), known as a CaaX box (where C is cysteine, a is an aliphatic amino acid, and X can be any amino acid). Once the target protein binds to the FTase, the farnesyl group is transferred from farnesyl pyrophosphate (FPP), a prenyl diphosphate, to the cysteine residue within the CaaX box. Following farnesylation, the three terminal amino acids (aaX) of the target protein are often removed by a specific protease, called RCE1, resulting in a farnesylated protein with a hydrophobic C-terminus. This hydrophobic tail facilitates interactions with the membrane, promoting localization and anchoring of the protein to the plasma membrane or other cellular compartments. Farnesylation plays a vital role in a wide array of cellular processes, including signal transduction, membrane trafficking, cytoskeletal organization, and cell growth. For instance, Ras proteins, key regulators of cell growth and proliferation, require farnesylation for their proper localization and signaling activity. Similarly, lamin A, a protein involved in nuclear envelope assembly, relies on farnesylation for its correct targeting and function. Moreover, farnesylation has been implicated in several diseases, including cancer and cardiovascular disorders. Targeting farnesylation has emerged as a promising therapeutic approach for various diseases, particularly cancer. Inhibitors of FTase, such as tipifarnib and lonafarnib, have shown antitumor activity in clinical trials, demonstrating the therapeutic potential of modulating this post-translational modification.'
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Proteins (4)

Compounds (31)