[Isoprenylation of proteins: what is its role?]

Abstract

The role of mevalonate in the control of DNA synthesis during the cell cycle has been studied and has lead to the detection of isoprenylated proteins. These proteins are modified by a polyisoprenoid (farnesyl or geranylgeranyl) moiety via a thioether linkage. This modification is required for the following steps of the post-translational maturation of these proteins: proteolysis of the last three C-terminal amino-acids and carboxymethylation of the Cysteine-COOH. The isoprenylation could play a role in the membrane localisation of these proteins. Farnesylated proteins present a C-terminal CAAX domain. Moreover, the farnesylation is required for their biological activity independently of the membrane localization (Prelamine A, p21ras(Val 12)). Among geranylgeranyl proteins, two types of C-terminal sequences have been found: one with the motif CAAX, the other with the motif CC or CXC. In the last type, both Cysteines are geranylgeranylated. The hydrophobicity of the geranylgeranyl moiety leads to the membrane attachment, without any specificity. Moreover, geranylgeranylation as well as farnesylation seem important for protein-protein interactions. Among the identified isoprenylated proteins, the lamins, gamma-subunits of G proteins and the numerous (if not all) members of the Ras superfamily were characterized. The exact role of isoprenylation is still uncertain but it seems to affect the membrane localization and the protein-protein interactions.