Targeting post-translational modification of transcription factors as cancer therapy
Abstract
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.
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Inhibition of HIF-α hydroxylation can be achieved using PHD inhibitors, including Roxadustat, which is approved in China and Europe for the treatment of renal anemia in CKD, and daprodustat, vadadustat, enarodustat and molidustat, which have been approved in Japan.
“As such, inhibition of HIF-α hydroxylation can be achieved using PHD inhibitors, such as Roxadustat, which is approved in China and Europe for the treatment of renal anemia in CKD, and other PHD inhibitors, daprodustat, vadadustat, enarodustat and molidustat, which have been approved in Japan.637–642”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [638]
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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
- Authors
- Qian, M., Yan, F., Yuan, T., Yang, B., He, Q., & Zhu, H.
- Affiliations
- Zhejiang University (CN)
- Corresponding author
- He, Qiaojun
- Zhu, Hong
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 25
- Issue
- 8
- Pages
- 1502-1512
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W3034816748
- Cited by
- 47
- References
- 66
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 9 · 2020: 1
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81830107, 81973349)
- Natural Science Foundation of Zhejiang Province (LR19H310002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- transcription factors, post-translational modification, cancer therapy, undruggable targets, protein stability, subcellular localization, protein-protein interaction, DNA binding, epigenetic regulation
- MeSH terms
- Acetylation, Animals, Humans, Methylation, Neoplasms, Phosphorylation, Protein Processing, Post-Translational, Transcription Factors
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