TiPARP forms nuclear condensates to degrade HIF-1α and suppress tumorigenesis.

Precisely controlling the activation of transcription factors is crucial for physiology. After a transcription factor is activated and carries out its transcriptional activity, it also needs to be properly deactivated. Here, we report a deactivation mechanism of HIF-1 and several other oncogenic transcription factors. HIF-1 promotes the transcription of an ADP ribosyltransferase, which serves to deactivate HIF-1. Mechanistically, forms distinct nuclear condensates or nuclear bodies in an ADP ribosylation-dependent manner. The TiPduanyu37 nuclear bodies recruit both HIF-1α and an E3 ubiquitin ligase HUWE1, which promotes the ubiquitination and degradation of HIF-1α. Similarly, TiPduanyu37 promotes the degradation of c-Myc and estrogen receptor. By suppressing HIF-1α and other oncogenic transcription factors, TiPduanyu37 exerts strong antitumor effects both in cell culture and in mouse xenograft models. Our work reveals TiPduanyu37 as a negative-feedback regulator for multiple oncogenic transcription factors, provides insights into the functions of protein ADP-ribosylation, and suggests activating TiPduanyu37 as an anticancer strategy. Copyright © 2020 the Author(s). Published by

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