Analysis of Human Thyroid Cancer-1 and Annexin V as Pro-Survival cDNA Sequences in Saccharomyces Cerevisiae

Abstract

Overexpressing a mouse Bax cDNA in yeast cells induces cell death. When heterologously expressed in yeast cells overexpression of a mouse cDNA encoding Bax, human Thyroid Cancer-1 (TC-1) or annexin V (ANXA5) suppresses the Bax induced cell death. My goal was to characterize the anti-Programmed Cell Death (anti-PCD) potential of these human cDNA sequences. In addition to rescuing Bax-expressing cells, I found that TC-1 and ANXA5 are pro-survival sequences that protect yeast from other death-inducing stresses including copper sulfate. TC-1 also prevented the deleterious effects caused by over-expression of a number of endogenous yeast pro-apoptotic sequences, including the YCA1 encoded metacaspase; the YBH3 encoded Bcl-2 Homology domain 3 protein, the NUC1 encoded DNase, as well as the apoptosis-inducing factor encoded by AIF1. Even though the protective effects were more pronounced in rescued cells over-expressing YBH3 and YCA1, TC-1 could still protect yeast mutant strains lacking YBH3 and YCA1 from the growth inhibitory effects of copper sulfate. Our results demonstrate that TC-1 and ANXA5 are pro-survival sequences that are able to attenuate stress-induced programmed cell death.