A Mechanism of ATF5 Anti-Apoptotic Action that Promotes Leukemia Cells Survival

Abstract

ATF5 transcription factor was found to play an essential role in hematopoietic cell survival and neuronal cell differentiation. Pro-survival activities of ATF5 are believed to be a result of its ability to inhibit apoptosis. Anti-apoptotic function of ATF5 is almost certainly carried out by regulating gene transcription, but information concerning its target genes has been missing. Here, we report the identification of cyclin D3 as an essential target of ATF5, and provide evidence that its upregulation is critical for the realization of ATF5-induced inhibition of apoptosis. Functional analysis confirmed the association of cyclin D3 with leukemia cells resistance to apoptosis and ATF5-induced splenic dysplasia in transgenic mice. These data link cyclin D3 cell cycle regulatory functions with the apoptotic machinery and reveal a potentially important facet of ATF5 biology.