Examining Farnesyltransferase Interaction With Cell-Permeable CaaX Peptides and the Role of the CaaX Motif in Biological Activity.

ABSTRACT: Recently, we presented cell-permeable CaaX peptides as versatile tools to study intracellular prenylation of proteins. These peptides consist of a cell-penetrating peptide (CPP) and a C-terminal CaaX motif derived from Ras proteins and demonstrated high cellular accumulation and the ability to influence Ras signaling in cancerous cells. Here, we aimed to gain a deeper insight into how such cell-permeable CaaX peptides, particularly the KRas4B-derived CaaX-1 peptide, interact with farnesyltransferase (FTase) and likely influence further intracellular processes. We show that CaaX-1 is farnesylated by FTase ex cellulo and that an intact CaaX motif is required for modification. A competition experiment revealed a slower farnesylation of CaaX-1 by FTase compared to a CaaX motif-containing contr

SUBMITTER: Klußmann M 

PROVIDER: S-EPMC11893521 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature