Journal of Inherited Metabolic Disease

, Volume 35, Issue 5, pp 917–926 | Cite as

Protein farnesylation and disease

  • Giuseppe NovelliEmail author
  • Maria Rosaria D’Apice
Original Article


Prenylation consists of the addition of an isoprenoid group to a cysteine residue located near the carboxyl terminal of a protein. This enzymatic posttranslational 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. This review attempts to summarise the basic aspects of protein isoprenylation and postprenylation, integrating our data with that observed in other studies to provide a comprehensive scenario of progeroid syndromes and the therapeutic avenues.


Zoledronic Acid Farnesyl Pyrophosphate Progeria Prenylated Protein LMNA Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Amino acids


Adenosine triphosphatase


C-cysteine, A-aliphatic amino acid, X-any amino acid


Cyclic guanosine monophosphate


Endoplasmic reticulum


Familial Dunnigan lipodystrophy


Farnesyl pyrophosphate


Farnesyl pyrophosphate synthase


Farnesyl transferase


Farnesyl transferase inhibitor


Guanosine diphosphate


Geranylgeranyl pyrophosphate


Geranylgeranyl transferase


Geranylgeranyl transferase I inhibitor


Guanosine triphosphate


Guanine nucleotide triphosphatases


Hutchinson-Gilford progeria syndrome


3-Hydroxy-3-methylglutaryl coenzyme A


heat shock protein 40


heat shock protein 70


Mandibuloacral dysplasia type A


Mandibuloacral dysplasia type B


Nitrogen bisphosphonate


Peroxisome proliferator-activated receptor gamma


Restrictive dermopathy


Sterol regulator element binding protein 1





This work was supported by the Italian Istituto Superiore di Sanità ‘Rare Diseases Italy-USA program’ [grant 526/D30] and AIFA [grant FARM7XE439].


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Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  1. 1.Department of Biopathology and Diagnostic ImagingUniversity of Tor VergataRomeItaly
  2. 2.San Pietro Fatebenefratelli HospitalRomeItaly
  3. 3.Fondazione Policlinico Tor VergataRomeItaly

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