ATPase family AAA domain-containing protein 2 (ATAD2): From an epigenetic modulator to cancer therapeutic target

ATPase family AAA domain-containing protein 2 (ATAD2) has been widely reported to be a new emerging oncogene that is closely associated with epigenetic modifications in human cancers. As a coactivator of transcription factors, ATAD2 can participate in epigenetic modifications and regulate the expression of downstream oncogenes or tumor suppressors, which may be supported by the enhancer of zeste homologue 2. Moreover, the dominant structure (AAA + ATPase and bromine domains) can make ATAD2 a potential therapeutic target in cancer, and some relevant small-molecule inhibitors, such as GSK8814 and AZ13824374, have also been discovered. Thus, in this review, we focus on summarizing the structural features and biological functions of ATAD2 from an epigenetic modulator to a cancer therapeutic target, and further discuss the existing small-molecule inhibitors targeting ATAD2 to improve potential cancer therapy. Together, these inspiring findings would shed new light on ATAD2 as a promising druggable target in cancer and provide a clue on the development of candidate anticancer drugs.

Automated summary

ATPase family AAA domain-containing protein 2 (ATAD2) is a new oncogene closely associated with epigenetic modifications in human cancers. It functions as a coactivator of transcription factors and regulates the expression of downstream oncogenes or tumor suppressors. The dominant structure of ATAD2 makes it a potential therapeutic target in cancer, and small-molecule inhibitors have been discovered. This review focuses on summarizing the structural features and biological functions of ATAD2 as well as the existing small-molecule inhibitors targeting ATAD2 for potential cancer therapy.