Farnesylation

Farnesol, a precursor in farnesylation.

Farnesyl pyrophosphate, one of the two substrates in farnesylation.

The farnesylation is a form of prenylation of proteins .

properties

Farnesylation is a post-translational modification of proteins through which, among other things, cytosolic proteins are attached to the cell membrane or to other biomembranes in a cell via the attached farnesyl group in the sense of a membrane anchor . The substrates in farnesylation are farnesyl pyrophosphate and one or two C -terminal cysteines on the protein to be modified. The leaving group in farnesylation is pyrophosphate . The enzyme farnesyl transferase catalyzes farnesylation, similar to geranylgeranylation .

Farnesylated proteins are e.g. B. Lamin A and Ras .

Faulty farnesylation of proteins is suspected to be involved in cancer , neurodegenerative diseases , retinitis pigmentosa and premature aging syndromes, among others . The inhibition of farnesyl transferases is being investigated in the treatment of cancer, progeria and infections with Trypanosoma brucei and Plasmodium falciparum .

literature

EM Storck, RA Serwa, EW Tate: Chemical proteomics: a powerful tool for exploring protein lipidation. In: Biochemical Society transactions . Volume 41, number 1, February 2013, pp. 56-61, doi : 10.1042 / BST20120283 , PMID 23356258 .

Individual evidence

↑ S. Reddy, L. Comai: Lamin A, farnesylation and aging. In: Experimental Cell Research . Volume 318, number 1, January 2012, pp. 1-7, doi : 10.1016 / j.yexcr.2011.08.009 , PMID 21871450 , PMC 4209918 (free full text).
↑ SM Sebti: Protein farnesylation: implications for normal physiology, malignant transformation, and cancer therapy. In: Cancer Cell . Volume 7, number 4, April 2005, pp. 297-300, doi : 10.1016 / j.ccr.2005.04.005 , PMID 15837619 .
↑ G. Novelli, MR D'Apice: Protein farnesylation and disease. In: Journal of Inherited Metabolic Disease . Volume 35, Number 5, September 2012, pp. 917-926, doi : 10.1007 / s10545-011-9445-y , PMID 22307208 .
^ AD Basso, P. Kirschmeier, WR Bishop: Lipid posttranslational modifications. Farnesyl transferase inhibitors. In: Journal of Lipid Research . Volume 47, Number 1, January 2006, pp. 15-31, doi : 10.1194 / jlr.R500012-JLR200 , PMID 16278491 .
↑ SG Young, SH Yang, BS Davies, HJ Jung, LG Fong: Targeting protein prenylation in progeria. In: Science Translational Medicine . Volume 5, number 171, February 2013, p. 171ps3, doi : 10.1126 / scitranslmed.3005229 , PMID 23390246 , PMC 3725554 (free full text).
^ RT Eastman, FS Buckner, K. Yokoyama, MH Gelb, WC Van Voorhis: Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation. In: Journal of Lipid Research. Volume 47, Number 2, February 2006, pp. 233-240, doi : 10.1194 / jlr.R500016-JLR200 , PMID 16339110 .

[1] S. Reddy, L. Comai: Lamin A, farnesylation and aging. In: Experimental Cell Research . Volume 318, number 1, January 2012, pp. 1-7, doi : 10.1016 / j.yexcr.2011.08.009 , PMID 21871450 , PMC 4209918 (free full text).

[2] SM Sebti: Protein farnesylation: implications for normal physiology, malignant transformation, and cancer therapy. In: Cancer Cell . Volume 7, number 4, April 2005, pp. 297-300, doi : 10.1016 / j.ccr.2005.04.005 , PMID 15837619 .

[3] G. Novelli, MR D'Apice: Protein farnesylation and disease. In: Journal of Inherited Metabolic Disease . Volume 35, Number 5, September 2012, pp. 917-926, doi : 10.1007 / s10545-011-9445-y , PMID 22307208 .

[4] AD Basso, P. Kirschmeier, WR Bishop: Lipid posttranslational modifications. Farnesyl transferase inhibitors. In: Journal of Lipid Research . Volume 47, Number 1, January 2006, pp. 15-31, doi : 10.1194 / jlr.R500012-JLR200 , PMID 16278491 .

[5] SG Young, SH Yang, BS Davies, HJ Jung, LG Fong: Targeting protein prenylation in progeria. In: Science Translational Medicine . Volume 5, number 171, February 2013, p. 171ps3, doi : 10.1126 / scitranslmed.3005229 , PMID 23390246 , PMC 3725554 (free full text).

[6] RT Eastman, FS Buckner, K. Yokoyama, MH Gelb, WC Van Voorhis: Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation. In: Journal of Lipid Research. Volume 47, Number 2, February 2006, pp. 233-240, doi : 10.1194 / jlr.R500016-JLR200 , PMID 16339110 .