Tat-D3S2 is a peptide derived from the sequence of the switch II region of the small GTPase DIRAS3, conjugated with the HIV-1 Tat protein transduction domain to enhance cellular permeability. DIRAS3 can induce autophagy and plays an important role in forming the autophagosome initiation complex (AIC) with beclin1. In disease states autophagy can protect cancer cells from acute starvation and enhance resistance to chemotherapy. Due to similarity to the binding region of DIRAS3, Tat-D3S2 can bind to beclin 1 and inhibit the beclin1 - DIRAS3 interaction necessary for the induction of autophagy, and in ovarian cancer cells where autophagy is induced by amino acid deprivation, Tat-D3S2 significantly inhibits cell viability.
