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MeSH Review

Protein Isoprenylation

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Disease relevance of Protein Isoprenylation

  • In the past two years, success has been achieved using a blocker of the farnesylation of Ras as a tumor inhibitor, a JAK-2 blocker as an efficient inhibitor of recurrent pre-B cell acute lymphoblastic leukemia, and a platelet-derived growth factor receptor kinase as a blocker of restenosis [1].
  • Biochemical studies implicate a highly conserved region involved in Rab binding, which is common to both GDI and the evolutionarily-related choroideremia gene product (CHM/REP) required for Rab prenylation [2].
  • We review three example of this inevitable post-cloning trend: first, the surprising relationship between mice with albino deletions and human hereditary tyrosinemia type I; second, the discovery that choroideremia is due to defect in prenylation; and third, fibrillin mutations in the Marfan syndrome [3].
  • These results implicate a defect in protein prenylation in the lovastatin-induced retinal degeneration, and suggest the presence of a dynamic pathway in the retina that requires isoprenylated proteins to maintain retinal cytoarchitecture [4].
  • Hutchinson-Gilford progeria syndrome (HGPS) is a devastating premature aging disease resulting from a mutation in the LMNA gene, which encodes nuclear lamins A and C. Lamin A is synthesized as a precursor (prelamin A) with a C-terminal CaaX motif that undergoes farnesylation, endoproteolytic cleavage, and carboxylmethylation [5].

High impact information on Protein Isoprenylation


Chemical compound and disease context of Protein Isoprenylation


Biological context of Protein Isoprenylation


Anatomical context of Protein Isoprenylation


Associations of Protein Isoprenylation with chemical compounds


Gene context of Protein Isoprenylation

  • Through the use of an in vitro assay with peptide substrates modeled after a presumptive a-mating pheromone precursor, it was discovered that mutations in DPR1-RAM1 cause a defect in the prenylation reaction [29].
  • A loss of function mutation occurs in the Rab27a gene in ashen (ash), whereas in gunmetal (gm) Rab27a dysfunction is secondary to a mutation in the alpha subunit of Rab geranylgeranyl transferase, an enzyme required for prenylation and activation of Rabs [30].
  • TOM2A encodes a 280 amino acid putative four-pass transmembrane protein with a C-terminal farnesylation signal, while TOM2B encodes a 122 amino acid basic protein [31].
  • In addition, inhibition of isoprenoid and cholesterol synthesis with the drug compactin also decreased [Val12]K-ras 4B protein isoprenylation and membrane association [32].
  • These results unequivocally demonstrate that isoprenylation, rather than palmitoylation, is essential for ras membrane binding and ras transforming activity [32].

Analytical, diagnostic and therapeutic context of Protein Isoprenylation


  1. Targeting signal transduction for disease therapy. Levitzki, A. Curr. Opin. Cell Biol. (1996) [Pubmed]
  2. Structural insights into the function of the Rab GDI superfamily. Wu, S.K., Zeng, K., Wilson, I.A., Balch, W.E. Trends Biochem. Sci. (1996) [Pubmed]
  3. Biochemical genetics: examples of life after cloning. McInnes, R.R., Byers, P.H. Curr. Opin. Genet. Dev. (1993) [Pubmed]
  4. In vivo requirement of protein prenylation for maintenance of retinal cytoarchitecture and photoreceptor structure. Pittler, S.J., Fliesler, S.J., Fisher, P.L., Keller, P.K., Rapp, L.M. J. Cell Biol. (1995) [Pubmed]
  5. Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford progeria syndrome. Mallampalli, M.P., Huyer, G., Bendale, P., Gelb, M.H., Michaelis, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Protein prenylation: molecular mechanisms and functional consequences. Zhang, F.L., Casey, P.J. Annu. Rev. Biochem. (1996) [Pubmed]
  7. Oxysterols: modulators of cholesterol metabolism and other processes. Schroepfer, G.J. Physiol. Rev. (2000) [Pubmed]
  8. The 70 kDa S6 kinase complexes with and is activated by the Rho family G proteins Cdc42 and Rac1. Chou, M.M., Blenis, J. Cell (1996) [Pubmed]
  9. Identification of the homologous beige and Chediak-Higashi syndrome genes. Barbosa, M.D., Nguyen, Q.A., Tchernev, V.T., Ashley, J.A., Detter, J.C., Blaydes, S.M., Brandt, S.J., Chotai, D., Hodgman, C., Solari, R.C., Lovett, M., Kingsmore, S.F. Nature (1996) [Pubmed]
  10. The effect of posttranslational modifications on the interaction of Ras2 with adenylyl cyclase. Kuroda, Y., Suzuki, N., Kataoka, T. Science (1993) [Pubmed]
  11. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Alsina, M., Fonseca, R., Wilson, E.F., Belle, A.N., Gerbino, E., Price-Troska, T., Overton, R.M., Ahmann, G., Bruzek, L.M., Adjei, A.A., Kaufmann, S.H., Wright, J.J., Sullivan, D., Djulbegovic, B., Cantor, A.B., Greipp, P.R., Dalton, W.S., Sebti, S.M. Blood (2004) [Pubmed]
  12. The third-generation bisphosphonate zoledronate synergistically augments the anti-Ph+ leukemia activity of imatinib mesylate. Kuroda, J., Kimura, S., Segawa, H., Kobayashi, Y., Yoshikawa, T., Urasaki, Y., Ueda, T., Enjo, F., Tokuda, H., Ottmann, O.G., Maekawa, T. Blood (2003) [Pubmed]
  13. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. Luckman, S.P., Hughes, D.E., Coxon, F.P., Graham, R., Russell, G., Rogers, M.J. J. Bone Miner. Res. (1998) [Pubmed]
  14. 17 beta-Estradiol overcomes a G1 block induced by HMG-CoA reductase inhibitors and fosters cell cycle progression without inducing ERK-1 and -2 MAP kinases activation. Bonapace, I.M., Addeo, R., Altucci, L., Cicatiello, L., Bifulco, M., Laezza, C., Salzano, S., Sica, V., Bresciani, F., Weisz, A. Oncogene (1996) [Pubmed]
  15. Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer. Kelland, L.R., Smith, V., Valenti, M., Patterson, L., Clarke, P.A., Detre, S., End, D., Howes, A.J., Dowsett, M., Workman, P., Johnston, S.R. Clin. Cancer Res. (2001) [Pubmed]
  16. Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Clarke, S. Annu. Rev. Biochem. (1992) [Pubmed]
  17. 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. Vorburger, K., Kitten, G.T., Nigg, E.A. EMBO J. (1989) [Pubmed]
  18. Pheromones trigger filamentous growth in Ustilago maydis. Spellig, T., Bölker, M., Lottspeich, F., Frank, R.W., Kahmann, R. EMBO J. (1994) [Pubmed]
  19. Molecular basis for Rab prenylation. Alory, C., Balch, W.E. J. Cell Biol. (2000) [Pubmed]
  20. A tagging-via-substrate technology for detection and proteomics of farnesylated proteins. Kho, Y., Kim, S.C., Jiang, C., Barma, D., Kwon, S.W., Cheng, J., Jaunbergs, J., Weinbaum, C., Tamanoi, F., Falck, J., Zhao, Y. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  21. Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia. Tolmachova, T., Anders, R., Abrink, M., Bugeon, L., Dallman, M.J., Futter, C.E., Ramalho, J.S., Tonagel, F., Tanimoto, N., Seeliger, M.W., Huxley, C., Seabra, M.C. J. Clin. Invest. (2006) [Pubmed]
  22. Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes. Alexandrov, K., Horiuchi, H., Steele-Mortimer, O., Seabra, M.C., Zerial, M. EMBO J. (1994) [Pubmed]
  23. ras isoprenylation is required for ras-induced but not for NGF-induced neuronal differentiation of PC12 cells. Qiu, M.S., Pitts, A.F., Winters, T.R., Green, S.H. J. Cell Biol. (1991) [Pubmed]
  24. Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells. James, G.L., Goldstein, J.L., Brown, M.S., Rawson, T.E., Somers, T.C., McDowell, R.S., Crowley, C.W., Lucas, B.K., Levinson, A.D., Marsters, J.C. Science (1993) [Pubmed]
  25. Isoprenoid metabolism is required for stimulation of the respiratory burst oxidase of HL-60 cells. Bokoch, G.M., Prossnitz, V. J. Clin. Invest. (1992) [Pubmed]
  26. In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. Bordier, B.B., Ohkanda, J., Liu, P., Lee, S.Y., Salazar, F.H., Marion, P.L., Ohashi, K., Meuse, L., Kay, M.A., Casey, J.L., Sebti, S.M., Hamilton, A.D., Glenn, J.S. J. Clin. Invest. (2003) [Pubmed]
  27. Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. Agarwal, B., Rao, C.V., Bhendwal, S., Ramey, W.R., Shirin, H., Reddy, B.S., Holt, P.R. Gastroenterology (1999) [Pubmed]
  28. 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Kusama, T., Mukai, M., Iwasaki, T., Tatsuta, M., Matsumoto, Y., Akedo, H., Inoue, M., Nakamura, H. Gastroenterology (2002) [Pubmed]
  29. Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein. Schafer, W.R., Trueblood, C.E., Yang, C.C., Mayer, M.P., Rosenberg, S., Poulter, C.D., Kim, S.H., Rine, J. Science (1990) [Pubmed]
  30. Rab27a is required for regulated secretion in cytotoxic T lymphocytes. Stinchcombe, J.C., Barral, D.C., Mules, E.H., Booth, S., Hume, A.N., Machesky, L.M., Seabra, M.C., Griffiths, G.M. J. Cell Biol. (2001) [Pubmed]
  31. Arabidopsis TOBAMOVIRUS MULTIPLICATION (TOM) 2 locus encodes a transmembrane protein that interacts with TOM1. Tsujimoto, Y., Numaga, T., Ohshima, K., Yano, M.A., Ohsawa, R., Goto, D.B., Naito, S., Ishikawa, M. EMBO J. (2003) [Pubmed]
  32. Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation. Jackson, J.H., Cochrane, C.G., Bourne, J.R., Solski, P.A., Buss, J.E., Der, C.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  33. Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. Cohen, S.J., Ho, L., Ranganathan, S., Abbruzzese, J.L., Alpaugh, R.K., Beard, M., Lewis, N.L., McLaughlin, S., Rogatko, A., Perez-Ruixo, J.J., Thistle, A.M., Verhaeghe, T., Wang, H., Weiner, L.M., Wright, J.J., Hudes, G.R., Meropol, N.J. J. Clin. Oncol. (2003) [Pubmed]
  34. The farnesyl protein transferase inhibitor BZA-5B blocks farnesylation of nuclear lamins and p21ras but does not affect their function or localization. Dalton, M.B., Fantle, K.S., Bechtold, H.A., DeMaio, L., Evans, R.M., Krystosek, A., Sinensky, M. Cancer Res. (1995) [Pubmed]
  35. Biochemical characterization and subcellular localization of the mouse retinitis pigmentosa GTPase regulator (mRpgr). Yan, D., Swain, P.K., Breuer, D., Tucker, R.M., Wu, W., Fujita, R., Rehemtulla, A., Burke, D., Swaroop, A. J. Biol. Chem. (1998) [Pubmed]
  36. The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity. Basso, A.D., Mirza, A., Liu, G., Long, B.J., Bishop, W.R., Kirschmeier, P. J. Biol. Chem. (2005) [Pubmed]
  37. Expression and mutagenesis of mouse rod photoreceptor cGMP phosphodiesterase. Qin, N., Baehr, W. J. Biol. Chem. (1994) [Pubmed]
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