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Journal of Inherited Metabolic Disease

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

Protein farnesylation and disease

  • Giuseppe Novelli
  • Maria Rosaria D’Apice
Original Article

Abstract

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.

Keywords

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.

Abbreviations

aa

Amino acids

ATPase

Adenosine triphosphatase

CAAX

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

cGMP

Cyclic guanosine monophosphate

ER

Endoplasmic reticulum

FPLD2

Familial Dunnigan lipodystrophy

FPP

Farnesyl pyrophosphate

FPPase

Farnesyl pyrophosphate synthase

FTase

Farnesyl transferase

FTI

Farnesyl transferase inhibitor

GDP

Guanosine diphosphate

GGPP

Geranylgeranyl pyrophosphate

GGTase

Geranylgeranyl transferase

GGTI

Geranylgeranyl transferase I inhibitor

GTP

Guanosine triphosphate

GTPases

Guanine nucleotide triphosphatases

HGPS

Hutchinson-Gilford progeria syndrome

HMG-CoA

3-Hydroxy-3-methylglutaryl coenzyme A

Hsp40

heat shock protein 40

Hsp70

heat shock protein 70

MADA

Mandibuloacral dysplasia type A

MADB

Mandibuloacral dysplasia type B

NBP

Nitrogen bisphosphonate

PPARγ

Peroxisome proliferator-activated receptor gamma

RD

Restrictive dermopathy

SREBP1

Sterol regulator element binding protein 1

S

Statin

Notes

Acknowledgements

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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© 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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