Exploitation of EP300 and CREBBP Lysine Acetyltransferases by Cancer
- 1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, California 90095
- 2Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, California 90095
- 3Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095
- 4Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California, Los Angeles, California 90095
- Correspondence: skurdistani{at}mednet.ucla.edu
Abstract
p300 and CREB-binding protein (CBP), two homologous lysine acetyltransferases in metazoans, have a myriad of cellular functions. They exert their influence mainly through their roles as transcriptional regulators but also via nontranscriptional effects inside and outside of the nucleus on processes such as DNA replication and metabolism. The versatility of p300/CBP as molecular tools has led to their exploitation by viral oncogenes for cellular transformation and by cancer cells to achieve and maintain an oncogenic phenotype. How cancer cells use p300/CBP in their favor varies depending on the cellular context and is evident by the growing list of loss- and gain-of-function genetic alterations in p300 and CBP in solid tumors and hematological malignancies. Here, we discuss the biological functions of p300/CBP and how disruption of these functions by mutations and alterations in expression or subcellular localization contributes to the cancer phenotype.
