Assessing the effi cacy of protein farnesyltransferase inhibitors in mouse models of progeria

Journal of Lipid Research

Volumn 51, Issue 2, 2010, Pages 400-405

  Yang, Shao H ^a   Chang, Sandy Y ^a   Andres, Douglas A ^b   Spielmann, H Peter ^b   Young, Stephen G ^a,c   Fong, Loren G ^a  

^a Departments of Human Genetics   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Aging; Farnesylation; Knock in mice; Lamin A; Posttranslational modifi cations; Protein farnesyltransferase; Protein prenylation

Indexed keywords

ABT 100; LAMIN A; PROGERIN; PROTEIN DERIVATIVE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG; ABT-100; ENZYME INHIBITOR; FARNESYL TRANS TRANSFERASE; IMIDAZOLE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG TREATMENT FAILURE; FEMALE; MALE; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROGERIA; PROTEIN MODIFICATION; ADIPOSE TISSUE; ANIMAL; BODY WEIGHT; DISEASE MODEL; DRUG ANTAGONISM; ENZYMOLOGY; FIBROBLAST; METABOLISM; PATHOLOGY; PRENYLATION; SURVIVAL; TIME;

ADIPOSE TISSUE; ANIMALS; BODY WEIGHT; DISEASE MODELS, ANIMAL; ENZYME INHIBITORS; FARNESYLTRANSTRANSFERASE; FEMALE; FIBROBLASTS; IMIDAZOLES; MALE; MICE; PHENOTYPE; PRENYLATION; PROGERIA; SURVIVAL ANALYSIS; TIME FACTORS;

EID: 77949527805     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M002808     Document Type: Article

References (21)

1. Eriksson, M., W. T. Brown, L. B. Gordon, M. W. Glynn, J. Singer, L. Scott, M. R. Erdos, C. M. Robbins, T. Y. Moses, P. Berglund, et al. 2003. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 423: 293-298.
2. de Sandre-Giovannoli, A., R. Bernard, P. Cau, C. Navarro, J. Amiel, I. Boccaccio, S. Lyonnet, C. L. Stewart, A. Munnich, M. Le Merrer, et al. 2003. Lamin A truncation in Hutchinson-Gilford progeria. Science. 300: 2055.
3. Young, S. G., L. G. Fong, and S. Michaelis. 2005. 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.
4. Dechat, T., T. Shimi, S. Adam, A. Rusinol, D. Andres, H. Spielmann, M. Sinensky, and R. Goldman. 2007. Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc. Natl. Acad. Sci. USA. 104: 4955-4960.
5. Goldman, R. D., D. K. Shumaker, M. R. Erdos, M. Eriksson, A. E. Goldman, L. B. Gordon, Y. Gruenbaum, S. Khuon, M. Mendez, R. Varga, et al. 2004. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford pro-geria syndrome. Proc. Natl. Acad. Sci. USA. 101: 8963-8968.
6. Yang, S. H., M. O. Bergo, J. I. Toth, X. Qiao, Y. Hu, S. Sandoval, M. Meta, P. Bendale, M. H. Gelb, S. G. Young, et al. 2005. Blocking protein farnesyltransferase improves nuclear blebbing in mouse fi broblasts with a targeted Hutchinson-Gilford progeria syndrome mutation. Proc. Natl. Acad. Sci. USA. 102: 10291-10296.
7. Scaffi di, P., and T. Misteli. 2005. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat. Med. 11: 440-445.
8. Toth, J. I., S. H. Yang, X. Qiao, A. P. Beigneux, M. H. Gelb, C. L. Moulson, J. H. Miner, S. G. Young, and L. G. Fong. 2005. Blocking protein farnesyltransferase improves nuclear shape in fi broblasts from humans with progeroid syndromes. Proc. Natl. Acad. Sci. USA. 102: 12873-12878.
9. Mallampalli, M. P., G. Huyer, P. Bendale, M. H. Gelb, and S. Michaelis. 2005. Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson-Gilford pro-geria syndrome. Proc. Natl. Acad. Sci. USA. 102: 14416-14421.
10. Capell, B. C., M. R. Erdos, J. P. Madigan, J. J. Fiordalisi, R. Varga, K. N. Conneely, L. B. Gordon, C. J. Der, A. D. Cox, and F. S. Collins. 2005. Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc. Natl. Acad. Sci. USA. 102: 12879-12884.
11. Glynn, M. W., and T. W. Glover. 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.
12. Yang, S. H., M. Meta, X. Qiao, D. Frost, J. Bauch, C. Coffi nier, S. Majumdar, M. O Bergo, S. G. Young, and L. G. Fong. 2006. Treatment with a protein farnesyltransferase inhibitor improves disease phenotypes in mice with a targeted Hutchinson-Gilford progeria syndrome mutation. J. Clin. Invest. 116: 2115-2121.
13. Fong, L. G., D. Frost, M. Meta, X. Qiao, S. Yang, C. Coffi nier, and S. Young. 2006. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science. 311: 1621-1623.
14. Yang, S. H., X. Qiao, L. G. Fong, and S. G. Young. 2008. Treatment with a farnesyltransferase inhibitor improves survival in mice with a Hutchinson-Gilford progeria syndrome mutation. Biochim. Biophys. Acta. 1781: 36-39.
15. Yang, S. H., D. A. Andres, H. P. Spielmann, S. G. Young, and L. G. Fong. 2008. Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated. J. Clin. Invest. 118: 3291-3300.
16. Kohl, N. E., F. R. Wilson, S. D. Mosser, E. Giuliani, S. J. DeSolms, M. W. Conner, N. J. Anthony, W. J. Holtz, R. P. Gomez, T-J. Lee, et al. 1994. Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. Proc. Natl. Acad. Sci. USA. 91: 9141-9145.
17. Sebti, S. M., and A. D. Hamilton. 2000. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies. Oncogene. 19: 6584-6593.
18. Ferguson, D., L. E. Rodriguez, J. P. Palma, M. Refi ci, K. Jarvis, J. O'Connor, G. M. Sullivan, D. Frost, K. Marsh, J. Bauch, et al. 2005. Antitumor activity of orally bioavailable farnesyltransferase inhibitor, ABT-100, is mediated by antiproliferative, proapoptotic, and antiangiogenic effects in xenograft models. Clin. Cancer Res. 11: 3045-3054.
19. Troutman, J. M., M. J. Roberts, D. A. Andres, and H. P. Spielmann. 2005. Tools to analyze protein farnesylation in cells. Bioconjug. Chem. 16: 1209-1217.
20. Yang, S. H., X. Qiao, E. Farber, S. Y. Chang, L. G. Fong, and S. G. Young. 2008. Eliminating the synthesis of mature lamin a reduces disease phenotypes in mice carrying a Hutchinson-Gilford progeria syndrome allele. J. Biol. Chem. 283: 7094-7099.
21. Varela, I., S. Pereira, A. P. Ugalde, C. L. Navarro, M. F. Suarez, P. Cau, J. Cadinanos, F. G. Osorio, N. Foray, J. Cobo, et al. 2008. Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat. Med. 14: 767-772.