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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

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  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]
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