ArticleChemical science2021
The effect of S427F mutation on RXRα activity depends on its dimeric partner.
Article in Chemical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed, 3 citations in OpenAlex.
- Free energy landscape of the PI3Kα C-terminal activation.Computational and structural biotechnology journal · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RXRs are nuclear receptors acting as transcription regulators that control key cellular processes in all tissues. All type II nuclear receptors require RXRs for transcriptional activity by forming heterodimeric complexes. Recent whole-exome sequencing studies have identified the RXRα S427F hotspot mutation in 5% of the bladder cancer patients, which is always located at the interface of RXRα with its obligatory dimerization partners. Here, we show that mutation of S427 deregulates transcriptional activity of RXRα dimers, albeit with diverse allosteric mechanisms of action depending on its dimeric partner. S427F acts by allosteric mechanisms, which range from inducing the collapse of the binding pocket to allosteric stabilization of active co-activator competent RXRα states. Unexpectedly, RXR S427F heterodimerization leads to either loss- or gain-of-function complexes, in both cases likely compromising its tumor suppressor activity. This is the first report of a cancer-associated single amino acid substitution that affects the function of the mutant protein variably depending on its dimerization partner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.