Skip to main content
SpringerLink
Log in

Protein farnesylation and disease

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

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

References

  • Agarwal AK, Fryns JP, Auchus RJ et al (2003) Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet 12:1995–2001

    Article  CAS  PubMed  Google Scholar 

  • Agrawal AG, Somani RR (2009) Farnesyltransferase inhibitor as anticancer agent. Mini Rev Med Chem 9:638–652

    Article  CAS  PubMed  Google Scholar 

  • Andrés V, González JM (2009) Role of A-type lamins in signaling, transcription, and chromatin organization. J Cell Biol 187:945–957

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Appels NM, Bolijn MJ, Chan K et al (2008) Phase I pharmacokinetic and pharmacodynamic study of the prenyl transferase inhibitor AZD3409 in patients with advanced cancer. Br J Cancer 98:1951–1958

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Armstrong SA, Hannah VC, Goldstein JL et al (1995) CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB. J Biol Chem 270:7864–7868

    Article  CAS  PubMed  Google Scholar 

  • Ashar HR, James L, Gray K et al (2000) Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. J Biol Chem 275:30451–30457

    Article  CAS  PubMed  Google Scholar 

  • Baron RA, Casey PJ (2004) Analysis of the kinetic mechanism of recombinant human isoprenylcysteine carboxylmethyltransferase (Icmt). BMC Biochem 5:19

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Beck LA, Hosick TJ, Sinensky M (1988) Incorporation of a product of mevalonic acid metabolism into proteins of Chinese hamster ovary cell nuclei. J Cell Biol 107:1307–1316

    Article  CAS  PubMed  Google Scholar 

  • Beck LA, Hosick TJ, Sinensky M (1990) Isoprenylation is required for the processing of the lamin A precursor. J Cell Biol 110:1489–1499

    Article  CAS  PubMed  Google Scholar 

  • Bergo MO, Leung GK, Ambroziak P et al (2000) Targeted inactivation of the isoprenylcysteine carboxyl methyltransferase gene causes mislocalization of K-Ras in mammalian cells. J Biol Chem 275:17605–17610

    Article  CAS  PubMed  Google Scholar 

  • Bergo MO, Leung GK, Ambroziak P et al (2001) Isoprenylcysteine carboxyl methyltransferase deficiency in mice. J Biol Chem 276:5841–5845

    Article  CAS  PubMed  Google Scholar 

  • Bergo MO, Ambroziak P, Gregory C et al (2002) Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation. Mol Cell Biol 22:171–181

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Blum R, Kloog Y (2005) Tailoring Ras-pathway-inhibitor combinations for cancer therapy. Drug Resist Updat 8:369–380

    Article  CAS  PubMed  Google Scholar 

  • Boettner B, Van Aelst L (2002) The role of Rho GTPases in disease development. Gene 286:155–174

    Article  CAS  PubMed  Google Scholar 

  • Broers JL, Machiels BM, Kuijpers HJ et al (1997) A- and B-type lamins are differentially expressed in normal human tissues. Histochem Cell Biol 107:505–517

    Article  CAS  PubMed  Google Scholar 

  • Broers JLV, Ramaekers FCS, Bonne G, Ben Yaou R, Hutchison CJ (2006) Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev 86:967–1008

    Article  CAS  PubMed  Google Scholar 

  • Burke B, Stewart CL (2002) Life at the edge: the nuclear envelope and human disease. Nat Rev Mol Cell Biol 3:575–585

    Article  CAS  PubMed  Google Scholar 

  • Cao H, Hegele RA (2000) Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 9:109–112

    Article  CAS  PubMed  Google Scholar 

  • Capanni C, Mattioli E, Columbaro M et al (2005) Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Hum Mol Genet 14:1489–1502

    Article  CAS  PubMed  Google Scholar 

  • Capell BC, Erdos MR, Madigan JP et al (2005) Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 102:12879–12884

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen Z, Otto JC, Bergo MO et al (2000) The C-terminal polylysine region and methylation of K-Ras are critical for the interaction between K-Ras and microtubules. J Biol Chem 275:41251–41257

    Article  CAS  PubMed  Google Scholar 

  • Coffinier C, Jung H-J, Li Z et al (2010) Direct synthesis of lamin A, bypassing prelamin A processing, causes misshapen nuclei in fibroblasts but no detectable pathology in mice. J Biol Chem 285:20818–20826

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • De Sandre-Giovannoli A, Bernard R, Cau P et al (2003) Lamin A truncation in Hutchinson-Gilford progeria. Science 300:2055

    Article  PubMed  Google Scholar 

  • Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 3:11–22

    Article  CAS  PubMed  Google Scholar 

  • Dunford JE, Thompson K, Coxon FP et al (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235–242

    CAS  PubMed  Google Scholar 

  • Eriksson M, Brown WT, Gordon LB et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293–298

    Article  CAS  PubMed  Google Scholar 

  • Feldman EJ (2006) Farnesyltransferase inhibitors in myelodysplastic syndrome. Curr Hematol Malign Rep 1:20–24

    Article  CAS  Google Scholar 

  • Filesi I, Gullotta F, Lattanzi G et al (2005) Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy. Physiol Genomics 23:150–158

    Article  CAS  PubMed  Google Scholar 

  • Fiordalisi JJ, Rushton BC, Tourssaint LF III et al (1999) High affinity for FTase and alternative prenylation contribute individually to K-Ras resistance to FTIs. Proc Am Assoc Can Res 40:521

    Google Scholar 

  • Fisher DZ, Chaudhary N, Blobel G (1986) cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. Proc Natl Acad Sci USA 83:6450–6454

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fong LG, Frost D, Meta M et al (2006) A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 311:1621–1623

    Article  CAS  PubMed  Google Scholar 

  • Fukada Y, Takao T, Ohguro H et al (1990) Farnesylated gamma-subunit of photoreceptor G protein indispensable for GTP-binding. Nature 346:658–660

    Article  CAS  PubMed  Google Scholar 

  • Furukawa K, Inagaki H, Hotta Y (1994) Identification and cloning of an mRNA coding for a germ cell-specific A-type lamin in mice. Exp Cell Res 212:426–430

    Article  CAS  PubMed  Google Scholar 

  • Gibbs JB, Oliff A, Kohl NE (1994) Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 77:177–178

    Article  Google Scholar 

  • Gibbs JB, Oliff A (1997) The potential of farnesyltransferase inhibitors as cancer chemotherapeutics. Annu Rev Pharmacol Toxicol 37:143–166

    Article  CAS  PubMed  Google Scholar 

  • Glynn MW, Glover TW (2005) Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition. Hum Mol Genet 14:2959–2969

    Article  CAS  PubMed  Google Scholar 

  • Glomset JA, Gelb MH, Farnsworth CC (1990) Prenyl proteins in eukaryotic cells: a new type of membrane anchor. Trends Biochem Sci 15:139–142

    Article  CAS  PubMed  Google Scholar 

  • Hancock JF, Cadwallader K, Paterson H et al (1991) A CAAX or a CAAL motif and a second signal are sufficient for plasma membrane targeting of ras proteins. EMBO J 10:4033–4039

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hannoush RN, Sun JL (2010) The chemical toolbox for monitoring protein fatty acylation and prenylation. Nat Chem Biol 6:498–506

    Article  CAS  PubMed  Google Scholar 

  • Harousseau JL, Martinelli G, Jedrzejczak WW et al (2009) A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older. Blood 114:1166–1173

    Article  CAS  PubMed  Google Scholar 

  • Hennekes H, Nigg EA (1994) The role of isoprenylation in membrane attachment of nuclear lamins. A single point mutation prevents proteolytic cleavage of the lamin A precursor and confers membrane binding properties. J Cell Sci 107:1019–1029

    CAS  PubMed  Google Scholar 

  • Holtz D, Tanaka RA, Hartwig J et al (1989) The CaaX motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope. Cell 59:969–977

    Article  CAS  PubMed  Google Scholar 

  • Houben F, Ramaekers FC, Snoeckx LH et al (2007) Role of nuclear lamina-cytoskeleton interactions in the maintenance of cellular strength. Biochim Biophys Acta 1773:675–686

    Article  CAS  PubMed  Google Scholar 

  • Inglese J, Glickman JF, Lorenz W et al (1992) Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase. J Biol Chem 267:1422–1425

    CAS  PubMed  Google Scholar 

  • Jackson JH, Li JW, Buss JE et al (1994) Polylysine domain of K-ras 4B protein is crucial for malignant transformation. Proc Natl Acad Sci USA 91:12730–12734

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • James GL, Goldstein JL, Brown MS (1995) Polylysine and CVIM sequences of K-RasB dictate specificity of prenylation and confer resistance to benzodiazepine peptidomimetics in vitro. J Biol Chem 266:14603–14610

    Google Scholar 

  • James G, Goldstein JL, Brown MS (1996) Resistance of K-RasBV12 proteins to farnesyltransferase inhibitors in Rat1 cells. Proc Natl Acad Sci USA 93:4454–4458

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kieran MW, Gordon L, Kleinman M (2007) New approaches to progeria. Pediatrics 120:834–841

    Article  PubMed  Google Scholar 

  • Kim E, Ambroziak P, Otto JC et al (1999) Disruption of the mouse Rce1 gene results in defective Ras processing and mislocalization of Ras within cells. J Biol Chem 274:8383–8390

    Article  CAS  PubMed  Google Scholar 

  • Kohl NE, Omer CA, Conner MW et al (1995) Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nat Med 1:792–797

    Article  CAS  PubMed  Google Scholar 

  • Krohne G, Waizenegger I, Hoger TH (1989) The conserved carboxy-terminal cysteine of nuclear lamins is essential for lamin association with the nuclear envelope. J Cell Biol 109:2003–2011

    Article  CAS  PubMed  Google Scholar 

  • Lai RK, Pérez-Sala D, Cañada FJ et al (1990) The subunit of transducin is farnesylated. Proc Natl Acad Sci USA 87:7673–7677

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lane KT, Beese LS (2006) Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res 47:681–699

    Article  CAS  PubMed  Google Scholar 

  • Lerner EC, Qian Y, Hamilton AD et al (1995) Disruption of oncogenic K-Ras4B processing and signaling by a potent geranylgeranyltransferase I inhibitor. J Biol Chem 270:26770–26773

    Article  CAS  PubMed  Google Scholar 

  • Leung KF, Baron R, Seabra MC (2006) Thematic review series: lipid posttranslational modifications. Geranylgeranylation of Rab GTPases. J Lipid Res 47:467–475

    Article  CAS  PubMed  Google Scholar 

  • Lin F, Worman HJ (1993) Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C. J Biol Chem 268:16321–16326

    CAS  PubMed  Google Scholar 

  • Lin F, Worman HJ (1995) Structural organization of the human gene (LMNB1) encoding nuclear lamin B1. Genomics 27:230–236

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Bryant MS, Chen J et al (1998) Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res 58:4947–4956

    CAS  PubMed  Google Scholar 

  • Liu M, Bryant MS, Chen J et al (1999) Effects of SCH 59228, an orally bioavailable farnesyl protein transferase inhibitor, on the growth of oncogene-transformed fibroblasts and a human colon carcinoma xenograft in nude mice. Cancer Chemother Pharmacol 43:50–58

    Article  CAS  PubMed  Google Scholar 

  • Luo L (2000) Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 1:173–178

    Article  CAS  PubMed  Google Scholar 

  • Lutz RJ, Trujillo MA, Denham KS et al (1992) Nucleoplasmic localization of prelamin A: implications for prenylation-dependent lamin A assembly into the nuclear lamina. Proc Natl Acad Sci USA 89:3000–3004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Machiels BM, Zorenc AHG, Endert JM et al (1996) An alternative splicing product of the lamin A/C gene lacks exon 10. J Biol Chem 271:9249–9253

    Article  CAS  PubMed  Google Scholar 

  • Magee T, Seabra MC (2005) Fatty acylation and prenylation of proteins: what’s hot in fat. Curr Opin Cell Biol 17:190–196

    Article  CAS  PubMed  Google Scholar 

  • Mallampalli MP, Huyer G, Bendale P et al (2005) Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 102:14416–14421

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maltese WA (1990) Posttranslational modification of proteins by isoprenoids in mammalian cells. FASEB J 4:3319–3328

    CAS  PubMed  Google Scholar 

  • Maurer-Stroh S, Koranda M, Benetka W et al (2007) Towards complete sets of farnesylated and geranylgeranylated proteins. PLoS Comput Biol 3(4):e66

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • McTaggart SJ (2006) Isoprenylated proteins. Cell Mol Life Sci 63:255–267

    Article  CAS  PubMed  Google Scholar 

  • McClintock D, Ratner D, Lokuge M et al (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One 2:e1269

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Melkonian KA, Ostermeyer AG, Chen JZ et al (1999) Role of lipid modifications intargeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J Biol Chem 274:3910–3917

    Article  CAS  PubMed  Google Scholar 

  • Miquel K, Pradines A, Sun J et al (1997) GGTI-228 induces G0-G1 block and apoptosis whereas FTI-227 causes G2-M enrichment in A549 cells. Cancer Res 57:1846–1850

    CAS  PubMed  Google Scholar 

  • Navarro CL, Cadinanos J, De Sandre-Giovannoli A et al (2005) Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of lamin A precursors. Hum Mol Genet 14:1503–1513

    Article  CAS  PubMed  Google Scholar 

  • Navarro CL, De Sandre-Giovannoli A, Bernard R et al (2004) Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet 13:2493–2503

    Article  CAS  PubMed  Google Scholar 

  • Novelli G, Muchir A, Sangiuolo F et al (2002) Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet 71:426–431

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Novelli G, D’Apice MR (2003) The strange case of the "lumper" lamin A/C gene and human premature ageing. Trends Mol Med 9:370–375

    Article  CAS  PubMed  Google Scholar 

  • Pereira-Leal JB, Hume AN, Seabra MC (2001) Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease. FEBS Lett 498:197–200

    Article  CAS  PubMed  Google Scholar 

  • Planey SL, Zacharias DA (2009) Palmitoyl acyltransferases, their substrates, and novel assays to connect them (review). Mol Membr Biol 26:14–31

    Article  CAS  PubMed  Google Scholar 

  • Prendergast GC, Davide JP, Lebowitz PF et al (1996) Resistance of a variant ras-transformed cell line to phenotypic reversion by farnesyl transferase inhibitors. Cancer Res 56:2626–2632

    CAS  PubMed  Google Scholar 

  • Ravoet C, Mineur P, Robin V et al (2008) Farnesyl transferase inhibitor (lonafarnib) in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia: a phase II study. Ann Hematol 87:881–885

    Article  CAS  PubMed  Google Scholar 

  • Reiss Y, Goldstein JL, Seabra MC et al (1990) Inhibitors of purified p21ras farnesyl: protein transferase by cys-AAX tetrapeptides. Cell 62:81–88

    Article  CAS  PubMed  Google Scholar 

  • Reiss Y, Stradley SJ, Gierasch LM et al (1991) Sequence requirement for peptide recognition by rat brain p21ras protein farnesyltransferase. Proc Natl Acad Sci USA 88:732–736

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Repasky GA, Chenette EJ, Der CJ (2004) Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis? Trends Cell Biol 14:639–647

    Article  CAS  PubMed  Google Scholar 

  • Resh MD (2006) Trafficking and signaling by fatty-acylated and prenylated proteins. Nat Chem Biol 2:584–590

    Article  CAS  PubMed  Google Scholar 

  • Scheffzek K, Stephan I, Jensen ON et al (2000) The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI. Nat Struct Biol 7:122–126

    Article  CAS  PubMed  Google Scholar 

  • Shackleton S, Lloyd DJ, Jackson SN et al (2000) LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet 24:153–156

    Article  CAS  PubMed  Google Scholar 

  • Sinensky M, Fantle K, Trujillo M et al (1994) The processing pathway of prelamin A. J Cell Sci 107:61–67

    CAS  PubMed  Google Scholar 

  • Sinensky M (2000a) Recent advances in the study of prenylated proteins. Biochim Biophys Acta 1484:93–106

    Article  CAS  PubMed  Google Scholar 

  • Sinensky M (2000b) Functional aspects of polyisoprenoid protein substituents: roles in protein-protein interaction and trafficking. Biochim Biophys Acta 1529:203–209

    Article  CAS  PubMed  Google Scholar 

  • Sousa SF, Fernandes PA, Ramos MJ (2008) Farnesyltransferase inhibitors: a detailed chemical view on an elusive biological problem. Curr Med Chem 15:1478–1492

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Qian Y, Hamilton AD et al (1998) Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts. Oncogene 16:1467–1473

    Article  CAS  PubMed  Google Scholar 

  • Takai Y, Sasaki T, Matozaki T (2001) Small GTP-binding proteins. Physiol Rev 81:153–208

    CAS  PubMed  Google Scholar 

  • Tamanoi F, Gau CL, Jiang C et al (2001) Protein farnesylation in mammalian cells: effects of farnesyltransferase inhibitors on cancer cells. Cell Mol Life Sci 58:1636–1649

    Article  CAS  PubMed  Google Scholar 

  • Toth JI, Yang SH, Qiao X et al (2005) Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc Natl Acad Sci USA 102:12873–12878

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tsimberidou AM, Chandhasin C, Kurzrock R (2010) Farnesyltransferase inhibitors: where are we now? Expert Opin Investig Drugs 19:1569–1580

    Article  CAS  PubMed  Google Scholar 

  • Vorburger K, Kitten GT, Nigg EA (1989) Modification of nuclear lamin proteins by a mevalonic acid derivative occurs in reticulocyte lysates and requires the cysteine residue of the C-terminal CXXM motif. EMBO J 8:4007–4013

    CAS  PubMed Central  PubMed  Google Scholar 

  • Varela I, Pereira S, Ugalde AP et al (2008) Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med 14:767–772

    Article  CAS  PubMed  Google Scholar 

  • Vigouroux C, Auclair M, Dubosclard E, Pouchelet M, Capeau J (2001) Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene. J Cell Sci 114:4459–4468

    CAS  PubMed  Google Scholar 

  • Vogt A, Sun J, Qian Y et al (1997) The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p1WAF1/CIP1/SDI1 in a p53-independent manner. J Biol Chem 272:27224–27229

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Sebti SM (2005) Palmitoylated cysteine 192 is required for RhoB tumor suppressive and apoptotic activities. J Biol Chem 280:19243–19249

    Article  CAS  PubMed  Google Scholar 

  • Winter-Vann AM, Casey PJ (2005) Post-prenylation processing enzymes as new targets in oncogenesis. Nat Rev Cancer 5:405–412

    Article  CAS  PubMed  Google Scholar 

  • Yang SH, Bergo MO, Toth JI et al (2005) Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation. Proc Natl Acad Sci USA 102:10291–10296

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yang SH, Meta M, Qiao X et al (2006) A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation. J Clin Invest 116:2115–2121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yang SH, Qiao X, Fong LG et al (2008) Treatment with a farnesyltransferase inhibitor improves survival in mice with a Hutchinson-Gilford progeria syndrome mutation. Biochim Biophys Acta 1781:36–39

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

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

Author information

Authors and Affiliations

  1. Department of Biopathology and Diagnostic Imaging, University of Tor Vergata, Via Montpellier 1, 00133, Rome, Italy

    Giuseppe Novelli & Maria Rosaria D’Apice

  2. San Pietro Fatebenefratelli Hospital, Rome, Italy

    Giuseppe Novelli

  3. Fondazione Policlinico Tor Vergata, Rome, Italy

    Maria Rosaria D’Apice

Authors
  1. Giuseppe Novelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Rosaria D’Apice
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuseppe Novelli.

Additional information

Communicated by: Niels Gregersen

Rights and permissions

Reprints and permissions

About this article

Cite this article

Novelli, G., D’Apice, M.R. Protein farnesylation and disease. J Inherit Metab Dis 35, 917–926 (2012). https://doi.org/10.1007/s10545-011-9445-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-011-9445-y

Keywords

Search

Navigation