Protein farnesylation and disease

  title={Protein farnesylation and disease},
  author={Giuseppe Novelli and Maria Rosaria D'Apice},
  journal={Journal of Inherited Metabolic Disease},
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… 
Production of Farnesylated and Methylated Proteins in an Engineered Insect Cell System.
Protocols for extending work to produce authentically modified KRAS protein to other farnesylated and methylated substrates are described.
A New Schema to Identify S-farnesyl Cysteine Prenylation Sites with Substrate Motifs
With a rapidly increasing number of experimentally verified S-farnesyl cysteine sites, there is still a lack of methods proposed for the prediction of S-methine prenylation sites, but this work is motivated in proposed new method for identifying S- farnesy cysteined prenolation sites.
Metabolic Stress Induces Caspase-3 Mediated Degradation and Inactivation of Farnesyl and Geranylgeranyl Transferase Activities in Pancreatic β-Cells
These findings provide the first evidence to suggest that metabolic stress induced dysfunction of the islet β-cell may, in part, be due to defective protein prenylation signaling pathway.
Increased RhoA Prenylation in the loechrig (loe) Mutant Leads to Progressive Neurodegeneration
It is shown that the loe mutation interferes with isoprenoid synthesis, leading to increased prenylation of the small GTPase Rho1, the fly orthologue of vertebrate RhoA, supporting findings in vertebrates that preNylation may play a role in neurodegenerative diseases like Alzheimer’s Disease.
Characterization of the Heavy-Metal-Associated Isoprenylated Plant Protein (HIPP) Gene Family from Triticeae Species
It is proved that HIPP1-V positively regulates Cd tolerance in common wheat and genome-wide overview of the Triticeae HIPP genes is provided.
Innovative Target Therapies Are Able to Block the Inflammation Associated with Dysfunction of the Cholesterol Biosynthesis Pathway
In this review, inhibitors of cholesterol synthesis, mitochondria-targeted drugs and inhibitors of the inflammasome are focused on.
Sterols and oxysterols in immune cell function
This work reviews recent literature reporting on the biological functions of sterol intermediates and oxysterols, acting through transcription factors such as the liver X receptors, sterol regulatory element–binding proteins and the G protein–coupled receptor EBI2, in regulating the differentiation and population expansion of cells of the innate and adaptive immune systems.
Protein Farnesylation on Nasopharyngeal Carcinoma, Molecular Background and Its Potential as a Therapeutic Target
An overview of the molecular pathogenesis of NPC in terms of the process of farnesylation is provided and the potential of anti-farnesylation therapy in the treatment of NPC is discussed.
Prenylation: From bacteria to eukaryotes
The bioinformatics analyses suggest the possibility of prenylation for a number of Francisella genus proteins, and the current state of the knowledge about the preNylation of eukaryotic and prokaryotic proteins and prenolation inhibitors is described.
Isolation and characterisation of cDNA encoding a wheat heavy metal-associated isoprenylated protein involved in stress responses.
Data indicate that TaHIPP1 is an important component in defence signalling pathways and may play a crucial role in the defence response of wheat to biotic and certain abiotic stresses.


Posttranslational modification of proteins by isoprenoids in mammalian cells
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  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1990
Isoprenylation plays a critical role in promoting the association of p21ras and the lamins with the cell membrane and nuclear envelope, respectively and should provide valuable new insight into the link between isoprenoid biosynthesis and cell growth.
Sequence dependence of protein isoprenylation.
Analysis of the kinetic mechanism of recombinant human isoprenylcysteine carboxylmethyltransferase (Icmt)
These studies establish that catalysis by human Icmt proceeds through an ordered sequential mechanism and provide a kinetic framework for analysis of specific inhibitors of this key enzyme.
Towards Complete Sets of Farnesylated and Geranylgeranylated Proteins
The prediction of the human proteins Prickle1, Prickle2, the BRO1 domain–containing FLJ32421 (termed BROFTI), and Rab28 (short isoform) as exclusive farnesyltransferase targets are verified and PRENbase, a database of large-scale predictions of protein prenylation substrates ranked by evolutionary conservation of the motif is introduced.
Post-prenylation-processing enzymes as new targets in oncogenesis
Findings indicate that the inhibition of these post-prenylation-processing steps — particularly that of ICMT-catalysed methylation — might provide a better approach to the control of cancer-cell proliferation.
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  • M. Sinensky
  • Biology, Chemistry
    Biochimica et biophysica acta
  • 2000
The gamma subunit of transducin is farnesylated.
This article shows that whole retinal cultures incorporate radioactive mevalonic acid into proteins of 23-26 kDa and one of 8 kDa, and concludes that transducin is the best understood G protein, both structurally and mechanistically, and the discovery that it is farnesylated should allow for a quantitative understanding of this post-translational modification.
Thematic review series: Lipid Posttranslational Modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I Published, JLR Papers in Press, February 13, 2006.
The structural biology of FTase and GGTase-I is examined to establish a framework for understanding the molecular basis of substrate specificity and mechanism and to assist in the design of inhibitors that could lead to treatments for cancer, viral infection, and a number of deadly parasitic diseases.
Targeted Inactivation of the Isoprenylcysteine Carboxyl Methyltransferase Gene Causes Mislocalization of K-Ras in Mammalian Cells*
It is concluded that carboxyl methylation of the isoprenylcysteine is important for proper K-Ras localization in mammalian cells.
Absence of the CAAX Endoprotease Rce1: Effects on Cell Growth and Transformation
The idea that interference with postisoprenylation processing retards cell growth, limits Ras-induced transformation, and sensitizes tumor cells to a farnesyltransferase inhibitor is supported.