Regulation of growth and survival of activated T cells by cell-transducing inhibitors of Ras

Abstract 

We describe the development of cell-penetrating inhibitors of Ras and study their ability to inhibit T cell activation. The inhibitors transduced T cells in a time and concentration-dependent manner and interacted with endogenous Ras. Anti-CD3/CD28-activated cells when treated with the inhibitors, exhibited a notable reduction in cell size, diminished proliferative capacity, and were more prone to apoptosis. Similarly, lymphocytes activated by antigen in vivo, exhibited accelerated apoptosis when treated with the inhibitors ex vivo. Our data reveal a pro-survival role for Ras in activated primary T cells and describe a new methodology for regulating its activity.

Structured summary

MINT-6802882: RAF1 (uniprotkb:P04049) physically interacts (MI:0218) with RAS (uniprotkb:P01112) by anti tag co-immunoprecipitation (MI:0007)

Abbreviations: RBD, Ras-binding domain of Raf-1, PTD, protein transduction domain, TCR, T cell antigen receptor, mBSA, methylated BSA, DTH, delayed type hypersensitivity

Keywords: Ras, Signalling inhibitor, Protein transduction domain, T cell activation, Apoptosis, T cell antigen receptor