Protein isoprenylation

EA2106 Protein isoprenylation

Protein isoprenylation is a post-translational lipidation common to eukaryotes. This process engages CaaX-protein prenyl transferases (CaaX-PTases) that recognize a tetrapeptide (called CaaX-box) localized on the carboxy-terminus of target proteins and attach a prenyl moiety to the Cysteine (illustrated in A). The prenyl consists in a farnesyl or a geranylgeranyl that is specifically linked to the CaaX-box by two different PTases: farnesyltransferase (PFT) and geranylgeranyltransferase type I (PGGT-I).

These protein lipidations have a determinant role in protein subcellular localization, protein interactions or enzyme activity, and contribute to the functional diversity of the cellular proteome. In plants, the characterization of CaaX-PTases knockout mutants in Arabidopsis highlighted the importance of protein isoprenylation in developmental processes as well as in plant responses to biotic and abiotic stress (B, example of the PFT mutant). However, the identification and the molecular characterization of the prenylated proteins engaged in these physiological processes are poorly documented and require the development of specific strategies.

In vivo tagging of prenylated proteins is facilitated by the use of modified prenylazide isoprenoids. This new approach, called tagging-via-substrate, allows the detection (shown in C) and further, the identification of prenylated proteins. This approach combined with the in silico analysis of proteins harboring a CaaX-box are powerful tools to unravel the role of isoprenylation in specific physiological contexts.

The CaaX-box sequence is critical for PTase activity and determines which prenyl is attached. Thus, the identity of the PTases engaged for the prenylation of a specific CaaX-box may be assessed through in vitro prenylation assays using fluorescent prenyl substrates (exemplified in D). Remarkably, protein isoprenylation is commonly associated to subcellular localization. This is visualized by YFP imagery, using WT or CaaX-PTases deficient lines expressing the CaaX-protein or a SaaX-mutated version (E). In addition, the physiological role of the proteins is further studied by reverse genetics.

Studies performed by the EA2106 BBV research team has highlighted a role of prenylated proteins in hormonal regulations and cellular metabolism. For instance, the regulation of secondary metabolite biosynthesis in Catharanthus roseus or seed lipid storage in Arabidopsis thaliana by methyljasmonate or abscisic acid, respectively, engages isoprenylation events. The identification of proteins targeted by the CaaX-PTase enzymes will help to decipher the molecular mechanisms that govern these important medicinal and agronomical traits.

Contact: Nathalie Guivarc'h 


Dutilleul, C., Ribeiro, I., Blanc, N., Nezames, C.D., Deng, X.W., Zglobicki, P., Palacio Barrera, A.M., AtehortĂąa, L, Courtois, M., Labas, V., Giglioli-Guivarc'h, N. & Ducos, E. (2015). ASG2 is a farnesylated DWD protein that acts as ABA negative regulator in Arabidopsis. Plant Cell Environment in press.

Courdavault, V., Clastre, M., Simkin, A. & Giglioli-Guivarc’h, N. (2013). Prenylated Proteins Are Required for Methyl-Jasmonate-Induced Monoterpenoid Indole Alkaloids Biosynthesis in Catharanthus roseus. In Isoprenoid Synth Plants Microorg SE  - 19, pp. 285–296. Edited by T. J. Bach & M. Rohmer. Springer New York.

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Courdavault, V., Burlat, V., St-Pierre, B. & Giglioli-Guivarc'h, N. (2009). Proteins prenylated by type I protein geranylgeranyltransferase act positively on the jasmonate signalling pathway triggering the biosynthesis of monoterpene indole alkaloids in Catharanthus roseus. Plant Cell Reports  28, 83-93.

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Courdavault, V., Burlat, V., St-Pierre, B. & Giglioli-Guivarc’h N.(2005) Characterisation of CaaX-prenyltransferases in Catharanthus roseus: relationships with the expression of genes involved in the early stages of monoterpenoid biosynthetic pathway. Plant Sci.  168, 1097–107.

Courdavault, V.,  Thiersault, M.,  Courtois, M.,  Gantet, P.,  Oudin, A.,  Doireau, P.,  St-Pierre, B. & Giglioli-Guivarc’h, N. (2005). CaaX-prenyltransferases are essential for expression of genes involved in the early stages of monoterpenoid biosynthetic pathway in Catharanthus roseus cells. Plant Mol. Biol. 57, 855–70.

Courdavault, V., Burlat, V., Gantet, P., St-Pierre, B. & Giglioli-Guivarc’h, N. (2005). Isolation of a cDNA encoding the α subunit of CaaX-prenyltransferases from Catharanthus roseus and the expression of the active recombinant protein farnesyltransferase. Cell. Mol. Biol. Lett. 10, 649-57.



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