AAA ATPase protein–protein interactions as therapeutic targets in cancer

Abstract

AAA ATPases are a conserved group of enzymes that couple ATP hydrolysis to diverse activities critical for cellular homeostasis by targeted protein–protein interactions. Some of these interactions are potential therapeutic targets because of their role in cancers which rely on increased AAA ATPase activities for maintenance of genomic stability. Two well-characterized members of this family are p97/VCP and RUVBL ATPases where there is a growing understanding of their structure and function, as well as an emerging landscape of selective inhibitors. Here we highlight recent progress in this field, with particular emphasis on structural advances enabled by cryo-electron microscopy (cryo-EM).