2016
DOI: 10.1084/jem.20151229
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Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4

Abstract: Lear et al. report a novel molecular pathway in which Fibrosis Inducing E3 Ligase 1 (FIEL1) regulates TGFβ and fibrosis pathway through SUMO-E3 ligase PIAS4. They also develop a small molecule inhibitor toward FIEL1 that is highly effective in ameliorating fibrosis in mice.

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Cited by 31 publications
(35 citation statements)
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“…For example, it was recently shown that BC-1485, a small molecule targeting the fibrosisinducing E3 ligase (FIEL1)-PIAS4 (protein inhibitor of activated STAT (signal transducer and activator of transcription) protein 4) pathway, which promotes TGFβ1 signalling, reduced the severity of fibrosis in bleomycin-induced lung injury 95 .…”
Section: Tgfβmentioning
confidence: 99%
“…For example, it was recently shown that BC-1485, a small molecule targeting the fibrosisinducing E3 ligase (FIEL1)-PIAS4 (protein inhibitor of activated STAT (signal transducer and activator of transcription) protein 4) pathway, which promotes TGFβ1 signalling, reduced the severity of fibrosis in bleomycin-induced lung injury 95 .…”
Section: Tgfβmentioning
confidence: 99%
“…This experiment suggests that the PPP1R11/TLR2 pathway is only active during S. aureus infection. It is likely that other regulators such as kinases are also involved in PPP1R11-driven TLR2 ubiquitination, which is common in E3 ligase substrate targeting (Chen et al, 2013; Lear et al, 2016). Further studies are warranted to investigate regulators that influence PPP1R11 expression and activity.…”
Section: Discussionmentioning
confidence: 99%
“…Through candidate screening we characterized a novel HECT E3 ligase, Fibrosis-Inducing E3 Ligase 1 (FIEL1), which regulates and ubiquitinates PIAS4 (18). The selective degradation of the PIAS4 isoform has downstream effects on SMAD signaling, as the depletion of FIEL1 encourages the repression of SMAD translocation and fibrotic gene expression.…”
mentioning
confidence: 99%