Targeting post-translational modification of transcription factors as cancer therapy

• Published in: Drug discovery today Vol. 25; no. 8; pp. 1502 - 1512
• Main Authors: Qian, Meijia, Yan, Fangjie, Yuan, Tao, Yang, Bo, He, Qiaojun, Zhu, Hong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2020
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2020.06.005

•Transcription factors are generally dysregulated in tumors.•Most oncogenic transcription factors are considered as “undruggable” targets.•Post-translational modifications dictate diverse aspects of transcription factors.•Agents that target transcription factors PTMs exert potent anti-tumor activities. Dysregulated transcription factors (TFs) fuel aberrant gene expression networks, resulting in cell overproliferation, migration, and immunosuppression. Given that TFs are regarded to have vital roles in tumors, various approaches are exploited to modulate their activities. Nevertheless, except for some ligand-binding nuclear receptors, most TFs are still considered ‘undruggable’ targets. Responding to extra- or intracellular stimuli, TFs are decorated with an array of post-translational modifications (PTMs) to regulate their subcellular localizations, protein–protein/DNA interactions, and stability. These PTMs orchestrate the multiple functions of TFs, thus offering numerous potential targets. In this review, we systematically review emerging concepts and effective agents in PTMs-associated TF-targeting, which could provide paradigms for cancer treatment.