Advertisement
J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on January 1, 2006

Papers In Press, published online ahead of print November 8, 2005
J. Lipid Res., doi:10.1194/jlr.R500012-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
R500012-JLR200v1
47/1/15    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Basso, A. D.
Right arrow Articles by Bishop, W. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Basso, A. D.
Right arrow Articles by Bishop, W. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Submitted on October 7, 2005
Revised on November 3, 2005
Accepted on November 7, 2005

Lipid posttranslational modifications: Farnesyl transferase inhibitors

Andrea D. Basso, Paul Kirschmeier, and W. Robert Bishop

Tumor Biology, Schering-Plough, Kenilworth, NJ 07033

Corresponding Author: andrea.basso{at}spcorp.com

Some proteins undergo post-translational modification by addition of an isoprenyl lipid (farnesyl- or geranylgeranyl-isoprenoid) to a cysteine residue proximal to the carboxy-terminus. Protein isoprenylation promotes membrane association and contributes to protein-protein interactions. Farnesylated proteins include small GTPases, tyrosine phosphatases, nuclear lamina, co-chaperones, and centromere-associated proteins. Prenylation is required for transforming activity of Ras. Due to the high frequency of Ras mutations in cancer, farnesyl transferase inhibitors (FTIs) were investigated as a means to antagonize Ras function. Evaluation of FTIs led to the finding that both K- and N-Ras are alternatively modified by GGTase-I in FTI-treated cells. Geranylgeranylated forms of Ras retain the ability to associate with the plasma membrane and activate substrates. Despite this, FTIs are effective at inhibiting growth of human tumor cells in vitro, suggesting activity is dependent on blocking farnesylation of other proteins. FTIs also inhibit the in vivo growth of human tumor xenografts and sensitize these models to chemotherapeutics, most notably taxanes. Several FTIs have entered clinical trials for various cancer indications. In some clinical settings, primarily hematologic malignancies, FTIs have displayed evidence of single-agent activity. Clinical studies in progress are exploring the antitumor activity of FTIs as single-agent and in combination. This review will summarize the basic biology of FTIs, their antitumor activity in preclinical models and the current status of clinical studies with these agents.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
N. M. Goldenberg and B. E. Steinberg
Surface Charge: A Key Determinant of Protein Localization and Function
Cancer Res., February 15, 2010; 70(4): 1277 - 1280.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Lee, S. Choi, G. Hallden, S. J. Yo, D. Schichnes, and G. W. Aponte
P2Y5 is a G{alpha}i, G{alpha}12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion
Am J Physiol Gastrointest Liver Physiol, October 1, 2009; 297(4): G641 - G654.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Zhou, C. C. Vos, A. Gjyrezi, M. Yoshida, F. R. Khuri, F. Tamanoi, and P. Giannakakou
The Protein Farnesyltransferase Regulates HDAC6 Activity in a Microtubule-dependent Manner
J. Biol. Chem., April 10, 2009; 284(15): 9648 - 9655.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. A. Baron, R. Tavare, A. C. Figueiredo, K. M. Blazewska, B. A. Kashemirov, C. E. McKenna, F. H. Ebetino, A. Taylor, M. J. Rogers, F. P. Coxon, et al.
Phosphonocarboxylates Inhibit the Second Geranylgeranyl Addition by Rab Geranylgeranyl Transferase
J. Biol. Chem., March 13, 2009; 284(11): 6861 - 6868.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
C. J. Balibar, X. Shen, and J. Tao
The Mevalonate Pathway of Staphylococcus aureus
J. Bacteriol., February 1, 2009; 191(3): 851 - 861.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. A. Hast and L. S. Beese
Structure of Protein Geranylgeranyltransferase-I from the Human Pathogen Candida albicans Complexed with a Lipid Substrate
J. Biol. Chem., November 14, 2008; 283(46): 31933 - 31940.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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, et al.
A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model
PNAS, October 14, 2008; 105(41): 15902 - 15907.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Eisenberg, K. Giehl, Y. I. Henis, and M. Ehrlich
Differential Interference of Chlorpromazine with the Membrane Interactions of Oncogenic K-Ras and Its Effects on Cell Growth
J. Biol. Chem., October 3, 2008; 283(40): 27279 - 27288.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
N. M. Jackson and T. A. Kocarek
Suppression of CYP2B Induction by Alendronate-Mediated Farnesyl Diphosphate Synthase Inhibition in Primary Cultured Rat Hepatocytes
Drug Metab. Dispos., October 1, 2008; 36(10): 2030 - 2036.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. W. Wojtkowiak, F. Fouad, D. T. LaLonde, M. D. Kleinman, R. A. Gibbs, J. J. Reiners Jr., R. F. Borch, and R. R. Mattingly
Induction of Apoptosis in Neurofibromatosis Type 1 Malignant Peripheral Nerve Sheath Tumor Cell Lines by a Combination of Novel Farnesyl Transferase Inhibitors and Lovastatin
J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 1 - 11.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. C. H. van der Hilst, B. Kluve-Beckerman, E. J. Bodar, J. W. M. van der Meer, J. P. H. Drenth, and A. Simon
Lovastatin inhibits formation of AA amyloid
J. Leukoc. Biol., May 1, 2008; 83(5): 1295 - 1299.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Shutes, C. Onesto, V. Picard, B. Leblond, F. Schweighoffer, and C. J. Der
Specificity and Mechanism of Action of EHT 1864, a Novel Small Molecule Inhibitor of Rac Family Small GTPases
J. Biol. Chem., December 7, 2007; 282(49): 35666 - 35678.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
W. C. Van Voorhis, K. L. Rivas, P. Bendale, L. Nallan, C. Horney, L. K. Barrett, K. D. Bauer, B. P. Smart, S. Ankala, O. Hucke, et al.
Efficacy, Pharmacokinetics, and Metabolism of Tetrahydroquinoline Inhibitors of Plasmodium falciparum Protein Farnesyltransferase
Antimicrob. Agents Chemother., October 1, 2007; 51(10): 3659 - 3671.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Raz, V. Nardi, M. Azam, J. Cortes, and G. Q. Daley
Farnesyl transferase inhibitor resistance probed by target mutagenesis
Blood, September 15, 2007; 110(6): 2102 - 2109.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Zheng, J. McKay, and J. E. Buss
H-Ras Does Not Need COP I- or COP II-dependent Vesicular Transport to Reach the Plasma Membrane
J. Biol. Chem., August 31, 2007; 282(35): 25760 - 25768.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Qiu, X. Liu, W. Zou, P. Yue, S. Lonial, F. R. Khuri, and S.-Y. Sun
The Farnesyltransferase Inhibitor R115777 Up-regulates the Expression of Death Receptor 5 and Enhances TRAIL-Induced Apoptosis in Human Lung Cancer Cells
Cancer Res., May 15, 2007; 67(10): 4973 - 4980.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
K. A. Grabinska, P. Magnelli, and P. W. Robbins
Prenylation of Saccharomyces cerevisiae Chs4p Affects Chitin Synthase III Activity and Chitin Chain Length
Eukaryot. Cell, February 1, 2007; 6(2): 328 - 336.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. L. Navarro, P. Cau, and N. Levy
Molecular bases of progeroid syndromes
Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R151 - R161.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
A. E. Rusinol and M. S. Sinensky
Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors.
J. Cell Sci., August 15, 2006; 119(Pt 16): 3265 - 3272.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. L. Kavanagh, J. E. Dunford, G. Bunkoczi, R. G. G. Russell, and U. Oppermann
The Crystal Structure of Human Geranylgeranyl Pyrophosphate Synthase Reveals a Novel Hexameric Arrangement and Inhibitory Product Binding
J. Biol. Chem., August 4, 2006; 281(31): 22004 - 22012.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
D. A. Mitchell, A. Vasudevan, M. E. Linder, and R. J. Deschenes
Thematic review series: Lipid Posttranslational Modifications. Protein palmitoylation by a family of DHHC protein S-acyltransferases
J. Lipid Res., June 1, 2006; 47(6): 1118 - 1127.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
L. P. Wright and M. R. Philips
Thematic review series: Lipid Posttranslational Modifications CAAX modification and membrane targeting of Ras
J. Lipid Res., May 1, 2006; 47(5): 883 - 891.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
K. T. Lane and L. S. Beese
Thematic review series: Lipid Posttranslational Modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I
J. Lipid Res., April 1, 2006; 47(4): 681 - 699.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
K. F. Leung, R. Baron, and M. C. Seabra
Thematic review series: Lipid Posttranslational Modifications. Geranylgeranylation of Rab GTPases
J. Lipid Res., March 1, 2006; 47(3): 467 - 475.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement