Publications by authors named "Bryant D Miller"
Lys ubiquitination is catalysed by E3 ubiquitin ligases and is central to the regulation of protein stability and cell signalling in normal and disease states. There are gaps in our understanding of E3 mechanisms, and here we use protein semisynthesis, chemical rescue, microscale thermophoresis and other biochemical approaches to dissect the role of catalytic base/acid function and conformational interconversion in HECT-domain E3 catalysis. We demonstrate that there is plasticity in the use of the terminal side chain or backbone carboxylate for proton transfer in HECT E3 ubiquitin ligase reactions, with yeast Rsp5 orthologues appearing to be possible evolutionary intermediates.
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- The LINE-1 retrotransposon is a significant genetic element in humans, contributing to about a third of our genome via a 'copy and paste' method driven by its enzyme, ORF2p, which is linked to diseases like cancer and autoimmunity.
- Recent studies using X-ray crystallography and cryo-electron microscopy have revealed new structural details of ORF2p, including previously unknown domains and a dynamic conformation that changes during the retrotransposition process.
- The findings enhance our understanding of L1 replication and its effects on immune responses, creating potential pathways for drug development targeting L1 and related cellular processes.
Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.
Cancer Discov
December 2023
Article Synopsis
- * The LINE-1 ORF1p protein is overexpressed in various cancers and has negligible expression in normal tissues, indicating its potential as a highly specific blood-based cancer biomarker.
- * Advanced digital immunoassays can detect low levels of ORF1p in plasma, showing promise for early detection of ovarian cancer and monitoring treatment responses in gastroesophageal cancers, suggesting it could be a valuable tool for cancer diagnosis and prognosis.
Article Synopsis
- * The Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is found to be overexpressed in various cancers but not in normal tissues, highlighting its potential as a specific cancer biomarker.
- * Researchers have developed highly sensitive digital immunoassays to detect ORF1p in blood samples, showing promise for early detection of ovarian cancer and improved monitoring of gastric and esophageal cancers, positioning it as a valuable multi-cancer biomarker.