Abstract LB-285: SAGA functions in development and disease

Abstract

Abstract Our research is focused on defining the functions of histone modifying enzymes in normal cells, so that we can understand how alterations in these activities contribute to tumor development or progression. Our recent studies on the SAGA complex, which houses both histone acetyltransferase (HAT) and deubiquitylase (DUB) activities, revealed that the Gcn5 HAT, is an important co-activator for Myc in regulating self-renewal of mouse ES cells. Gcn5 is also important for Myc functions as a Yamanaka factor in stimulating conversion of differentiated cells towards an induced pluripotent state. These developmental functions predict that Gcn5 will also be important during Myc functions as an oncogene. In support of this idea, recent studies reveal that deletion of Gcn5 delays lymphoma onset and more than doubles survival of Eμ-Myc mice. The SAGA DUB module is also implicated in cancer, as the USP22 catalytic subunit is overexpressed in several highly aggressive human tumors. We have created USP22 knock out mice to probe the functions of this DUB. Our data indicate that USP22 drives TGF-beta and receptor tyrosine kinase signaling pathways that are critical both to normal developmental processes and to oncogenesis. Altogether, our studies indicate that both Gcn5 and USP22 may provide unique targets for development of new cancer therapies. Note: This abstract was not presented at the meeting. Citation Format: Sharon Y. Dent, Aimee Farria, Evangelia Koutelou. SAGA functions in development and disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-285.