TF-DUBTACs Stabilize Tumor Suppressor Transcription Factors

Jing Liu, Xufen Yu, He Chen, H. Ümit Kaniskan, Ling Xie, Xian Chen, Jian Jin, Wenyi Wei

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Targeted protein degradation approaches have been widely used for degrading oncogenic proteins, providing a potentially promising therapeutic strategy for cancer treatment. However, approaches to targeting tumor suppressor proteins are very limited, and only a few agonists have been developed to date. Here, we report the development of a platform termed TF-DUBTAC, which links a DNA oligonucleotide to a covalent ligand of the deubiquitinase OTUB1 via a click reaction, to selectively stabilize tumor suppressor transcription factors. We developed three series of TF-DUBTACs, namely, FOXO-DUBTAC, p53-DUBTAC, and IRF-DUBTAC, which stabilize FOXO3A, p53, and IRF3 in cells, respectively, in an OTUB1-dependent manner. These results suggest that TF-DUBTAC is a generalizable platform to achieve selective stabilization of tumor suppressor transcription factors as a therapeutic means to suppress tumorigenesis.

Original languageEnglish
Pages (from-to)12934-12941
Number of pages8
JournalJournal of the American Chemical Society
Issue number28
StatePublished - 20 Jul 2022


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