Dataset Information

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

ABSTRACT: 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, TiPARP, which serves to deactivate HIF-1. Mechanistically, TiPARP forms distinct nuclear condensates or nuclear bodies in an ADP ribosylation-dependent manner. The TiPARP nuclear bodies recruit both HIF-1? and an E3 ubiquitin ligase HUWE1, which promotes the ubiquitination and degradation of HIF-1?. Similarly, TiPARP promotes the degradation of c-Myc and estrogen receptor. By suppressing HIF-1? and other oncogenic transcription factors, TiPARP exerts strong antitumor effects both in cell culture and in mouse xenograft models. Our work reveals TiPARP as a negative-feedback regulator for multiple oncogenic transcription factors, provides insights into the functions of protein ADP-ribosylation, and suggests activating TiPARP as an anticancer strategy.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7306777 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Zhang Lu L Cao Ji J Dong Longying L Lin Hening H

Proceedings of the National Academy of Sciences of the United States of America 20200601 24

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, TiPARP, which serves to deactivate HIF-1. Mechanistically, TiPARP forms distinct nuclear condensates or nuclear bodie ...[more]

PMID: 32482854

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Project description:Loss of larger consumers from stressed ecosystems can lead to trophic release of mid-level consumers that then impact foundation species, suppressing ecosystem function and resilience. For example, in coral reef ecosystems, outbreaks of coral predators like crown-of-thorns sea stars have been associated with fishing pressure and can dramatically impact the composition and persistence of corals. However, the ecological impacts, and consequences for management, of smaller, less obvious corallivores remain inadequately understood. We investigated whether reef state (coral vs. seaweed domination) influenced densities and size frequencies of the corallivorous gastropod Coralliophila violacea on its common host, the coral Porites cylindrica, within three pairs of small Marine Protected Areas (MPAs) and adjacent fished areas in Fiji. C. violacea densities were 5-35 times greater, and their size frequencies more broadly distributed, within seaweed-dominated fished areas than in adjacent MPAs dominated by corals. Tethering snails (4-9 mm in shell height) in place on their coral hosts indicated that suppression of snails in MPAs was due to predation, apparently by fishes. When tethered on the benthos (where they rarely occur), rather than on their host, mortality of larger snails (15.0-25.0 mm in shell height) was high in all areas, primarily due to hermit crabs killing them and occupying their shells. Because C. violacea is a sessile gastropod that feeds affixed to the base of corals and produces minimal visible damage, it has been considered a "prudent feeder" that minimally impacts its host coral. We assessed this over a 24-d feeding period in the field. Feeding by individual C. violacea reduced P. cylindrica growth by ~18-43% depending on snail size. Our findings highlight the considerable, but underappreciated, negative impacts of this common corallivore on degraded reefs. As reefs degrade and corals are lost, remaining corals (often species of Porites) may gain the full attention of elevated densities of coral consumers. This will further damage the remaining foundation species, suppressing the resilience of corals and enhancing the resilience of degraded, seaweed-dominated reefs.

Dataset Information

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

Publications

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

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