Targeting protein prenylation in progeria

Science Translational Medicine

Volumn 5, Issue 171, 2013, Pages

  Young, Stephen G ^a,b   Yang, Shao H ^a   Davies, Brandon S J ^a   Jung, Hea Jin ^b   Fong, Loren G ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LAMIN A; LONAFARNIB; PRAVASTATIN; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAPAMYCIN; RAS PROTEIN; ZOLEDRONIC ACID;

BIOACCUMULATION; CLINICAL FEATURE; DISEASE ACTIVITY; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; GENE; GENE FREQUENCY; GENE FUNCTION; GENE MUTATION; HETEROZYGOTE DETECTION; LAMIN A GENE; MOLECULAR PATHOLOGY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROGERIA; PROTEIN CLEAVAGE; PROTEIN MOTIF; PROTEIN PRENYLATION; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL NUCLEUS SHAPE; CLINICAL TRIALS AS TOPIC; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; HUMANS; LAMINS; PROGERIA; PROTEIN PRENYLATION;

EID: 84874088283     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3005229     Document Type: Review

References (39)

1. F. L. DeBusk, The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J. Pediatr. 80, 697-724 (1972).
2. L. B. Gordon, M. E. Kleinman, D. T. Miller, D. S. Neuberg, A. Giobbie-Hurder, M. Gerhard-Herman, L. B. Smoot, C. M. Gordon, R. Cleveland, B. D. Snyder, B. Fligor, W. R. Bishop, P. Statkevich, A. Regen, A. Sonis, S. Riley, C. Ploski, A. Correia, N. Quinn, N. J. Ullrich, A. Nazarian, M. G. Liang, S. Y. Huh, A. Schwartzman, M. W. Kieran, Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc. Natl. Acad. Sci. U.S.A. 109, 16666-16671 (2012).
3. M. Eriksson, W. T. Brown, L. B. Gordon, M. W. Glynn, J. Singer, L. Scott, M. R. Erdos, C. M. Robbins, T. Y. Moses, P. Berglund, A. Dutra, E. Pak, S. Durkin, A. B. Csoka, M. Boehnke, T. W. Glover, F. S. Collins, Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423, 293-298 (2003).
4. F. L. Zhang, P. J. Casey, Protein prenylation: Molecular mechanisms and functional consequences. Annu. Rev. Biochem. 65, 241-269 (1996).
5. G. L. James, J. L. Goldstein, M. S. Brown, T. E. Rawson, T. C. Somers, R. S. McDowell, C. W. Crowley, B. K. Lucas, A. D. Levinson, J. C. Marsters Jr., Benzodiazepine peptidomi-metics: Potent inhibitors of Ras farnesylation in animal cells. Science 260, 1937-1942 (1993).
6. S. G. Young, L. G. Fong, S. Michaelis, Prelamin A, Zmpste24, misshapen cell nuclei, and progeria - New evidence suggesting that protein farnesylation could be important for disease pathogenesis. J. Lipid Res. 46, 2531-2558 (2005).
7. M. Sinensky, K. Fantle, M. Trujillo, T. McLain, A. Kupfer, M. Dalton, The processing pathway of prelamin A. J. Cell Sci. 107, 61-67 (1994).
8. A. M. Pendás, Z. Zhou, J. Cadiñanos, J. M. P. Freije, J. Wang, K. Hultenby, A. Astudillo, A. Wernerson, F. Rodríguez, K. Tryggvason, C. López-Otín, Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nat. Genet. 31, 94-99 (2002).
9. M. O. Bergo, B. Gavino, J. Ross, W. K. Schmidt, C. Hong, L. V. Kendall, A. Mohr, M. Meta, H. Genant, Y. Jiang, E. R. Wisner, N. Van Bruggen, R. A. D. Carano, S. Michaelis, S. M. Griffey, S. G. Young, Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc. Natl. Acad. Sci. U.S.A. 99, 13049-13054 (2002).
10. C. L. Moulson, G. Go, J. M. Gardner, A. C. van der Wal, J. H. Smitt, J. M. van Hagen, J. H. Miner, Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy. J. Invest. Dermatol. 125, 913-919 (2005).
11. C. L. Moulson, L. G. Fong, J. M. Gardner, E. A. Farber, G. Go, A. Passariello, D. K. Grange, S. G. Young, J. H. Miner, Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes. Hum. Mutat. 28, 882-889 (2007).
12. L. G. Fong, J. K. Ng, M. Meta, N. Coté, S. H. Yang, C. L. Stewart, T. Sullivan, A. Burghardt, S. Majumdar, K. Reue, M. O. Bergo, S. G. Young, Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 101, 18111-18116 (2004).
13. S. H. Yang, M. O. Bergo, J. I. Toth, X. Qiao, Y. Hu, S. Sandoval, M. Meta, P. Bendale, M. H. Gelb, S. G. Young, L. G. Fong, Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation. Proc. Natl. Acad. Sci. U.S.A. 102, 10291-10296 (2005).
14. R. J. Lutz, M. A. Trujillo, K. S. Denham, L. Wenger, M. Sinensky, Nucleoplasmic localization of prelamin A: Implications for prenylation-dependent lamin A assembly into the nuclear lamina. Proc. Natl. Acad. Sci. U.S.A. 89, 3000-3004 (1992).
15. A. Muchir, J. Medioni, M. Laluc, C. Massart, T. Arimura, A. J. van der Kooi, I. Desguerre, M. Mayer, X. Ferrer, S. Briault, M. Hirano, H. J. Worman, A. Mallet, M. Wehnert, K. Schwartz, G. Bonne, Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations. Muscle Nerve 30, 444-450 (2004).
16. J. I. Toth, S. H. Yang, X. Qiao, A. P. Beigneux, M. H. Gelb, C. L. Moulson, J. H. Miner, S. G. Young, L. G. Fong, Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc. Natl. Acad. Sci. U.S.A. 102, 12873-12878 (2005).
17. S. H. Yang, M. Meta, X. Qiao, D. Frost, J. Bauch, C. Coffinier, S. Majumdar, M. O. Bergo, S. G. Young, L. G. Fong, A farne-syltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation. J. Clin. Invest. 116, 2115-2121 (2006).
18. C. Coffinier, H. J. Jung, Z. Li, C. Nobumori, U. J. Yun, E. A. Farber, B. S. Davies, M. M. Weinstein, S. H. Yang, J. Lammerding, J. N. Farahani, L. A. Bentolila, L. G. Fong, S. G. Young, 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 (2010).
19. B. S. Davies, R. H. Barnes 2nd, Y. Tu, S. Ren, D. A. Andres, H. P. Spielmann, J. Lammerding, Y. Wang, S. G. Young, L. G. Fong, An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria. Hum. Mol. Genet. 19, 2682-2694 (2010).
20. S. H. Yang, S. Y. Chang, S. Ren, Y. Wang, D. A. Andres, H. P. Spielmann, L. G. Fong, S. G. Young, Absence of progeria-like disease phenotypes in knock-in mice expressing a non-farnesylated version of progerin. Hum. Mol. Genet. 20, 436-444 (2011).
21. S. H. Yang, S. Y. Chang, Y. Tu, G. W. Lawson, M. O. Bergo, L. G. Fong, S. G. Young, Severe hepatocellular disease in mice lacking one or both CaaX prenyltransferases. J. Lipid Res. 53, 77-86 (2012).
22. L. G. Fong, D. Frost, M. Meta, X. Qiao, S. H. Yang, C. Coffinier, S. G. Young, A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 311, 1621-1623 (2006).
23. S. H. Yang, X. Qiao, L. G. Fong, S. G. Young, Treatment with a farnesyltransferase inhibitor improves survival in mice with a Hutchinson-Gilford progeria syndrome mutation. Biochim. Biophys. Acta 1781, 36-39 (2008).
24. B. C. Capell, M. Olive, M. R. Erdos, K. Cao, D. A. Faddah, U. L. Tavarez, K. N. Conneely, X. Qu, H. San, S. K. Ganesh, X. Chen, H. Avallone, F. D. Kolodgie, R. Virmani, E. G. Nabel, F. S. Collins, A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model. Proc. Natl. Acad. Sci. U.S.A. 105, 15902-15907 (2008).
25. S. H. Yang, D. A. Andres, H. P. Spielmann, S. G. Young, L. G. Fong, Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated. J. Clin. Invest. 118, 3291-3300 (2008).
26. H. J. Worman, L. G. Fong, A. Muchir, S. G. Young, Laminop-athies and the long strange trip from basic cell biology to therapy. J. Clin. Invest. 119, 1825-1836 (2009).
27. R. Lee, S. Y. Chang, H. Trinh, Y. Tu, A. C. White, B. S. Davies, M. O. Bergo, L. G. Fong, W. E. Lowry, S. G. Young, Genetic studies on the functional relevance of the protein prenyltransferases in skin keratinocytes. Hum. Mol. Genet. 19, 1603-1617 (2010).
28. S. H. Yang, S. Y. Chang, D. A. Andres, H. P. Spielmann, S. G. Young, L. G. Fong, Assessing the efficacy of protein farne-syltransferase inhibitors in mouse models of progeria. J. Lipid Res. 51, 400-405 (2010).
29. D. B. Whyte, P. Kirschmeier, T. N. Hockenberry, I. Nunez-Oliva, L. James, J. J. Catino, W. R. Bishop, J.-K. Pai, K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J. Biol. Chem. 272, 14459-14464 (1997).
30. I. Varela, S. Pereira, A. P. Ugalde, C. L. Navarro, M. F. Suárez, P. Cau, J. Cadiñanos, F. G. Osorio, N. Foray, J. Cobo, F. de Carlos, N. Lévy, J. M. Freije, C. López-Otín, Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat. Med. 14, 767-772 (2008).
31. B. C. Capell, M. R. Erdos, J. P. Madigan, J. J. Fiordalisi, R. Varga, K. N. Conneely, L. B. Gordon, C. J. Der, A. D. Cox, F. S. Collins, Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc. Natl. Acad. Sci. U.S.A. 102, 12879-12884 (2005).
32. J. Couzin-Frankel, Medicine. Drug trial offers uncertain start in race to save children with progeria. Science 337, 1594-1595 (2012).
33. P. Scaffidi, T. Misteli, Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat. Med. 11, 440-445 (2005).
34. L. G. Fong, T. A. Vickers, E. A. Farber, C. Choi, U. J. Yun, Y. Hu, S. H. Yang, C. Coffinier, R. Lee, L. Yin, B. S. Davies, D. A. Andres, H. P. Spielmann, C. F. Bennett, S. G. Young, Activating the synthesis of progerin, the mutant prelamin A in Hutchinson-Gilford progeria syndrome, with antisense oligonucleotides. Hum. Mol. Genet. 18, 2462-2471 (2009).
35. F. G. Osorio, C. L. Navarro, J. Cadiñanos, I. C. López-Mejía, P. M. Quirós, C. Bartoli, J. Rivera, J. Tazi, G. Guzmán, I. Varela, D. Depetris, F. de Carlos, J. Cobo, V. Andrés, A. De Sandre-Giovannoli, J. M. Freije, N. Lévy, C. López-Otín, Splicing-directed therapy in a new mouse model of human accelerated aging. Sci. Transl. Med. 3, 106ra107 (2011).
36. K. Cao, J. J. Graziotto, C. D. Blair, J. R. Mazzulli, M. R. Erdos, D. Krainc, F. S. Collins, Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells. Sci. Transl. Med. 3, 89ra58 (2011).
37. L. G. Fong, J. K. Ng, J. Lammerding, T. A. Vickers, M. Meta, N. Coté, B. Gavino, X. Qiao, S. Y. Chang, S. R. Young, S. H. Yang, C. L. Stewart, R. T. Lee, C. F. Bennett, M. O. Bergo, S. G. Young, Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J. Clin. Invest. 116, 743-752 (2006).
38. H. J. Jung, C. Coffinier, Y. Choe, A. P. Beigneux, B. S. Davies, S. H. Yang, R. H. Barnes 2nd, J. Hong, T. Sun, S. J. Pleasure, S. G. Young, L. G. Fong, Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA. Proc. Natl. Acad. Sci. U.S.A. 109, E423-E431 (2012).
39. X. Nissan, S. Blondel, C. Navarro, Y. Maury, C. Denis, M. Girard, C. Martinat, A. De Sandre-Giovannoli, N. Levy, M. Peschanski, Unique preservation of neural cells in Hutchinson-Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA. Cell Reports 2, 1-9 (2012).