A5014106434- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Trace Elements in Health
- Fibroblast Growth Factor Research
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Erythropoietin and Anemia Treatment
- Chronic Myeloid Leukemia Treatments
- Cancer-related gene regulation
- Proteoglycans and glycosaminoglycans research
- Mast cells and histamine
- Autophagy in Disease and Therapy
- Peroxisome Proliferator-Activated Receptors
- Chemokine receptors and signaling
- Neurological diseases and metabolism
- Glycosylation and Glycoproteins Research
Bristol-Myers Squibb (United States)
2020-2023
Pathways Behavioral Services
2014
The University of Texas Southwestern Medical Center
2009-2012
Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of genes responsible for uptake, release, use, and storage through actions regulatory proteins IRP1 IRP2. However, manner in which levels are sensed to affect IRP2 activity poorly understood. We found that an E3 ubiquitin ligase complex containing FBXL5 protein targets proteasomal degradation. The stability itself was regulated, accumulating under iron- oxygen-replete conditions degraded upon depletion....
Mammalian cells maintain iron homeostasis by sensing changes in bioavailable levels and promoting adaptive responses. FBXL5 is a subunit of an E3 ubiquitin ligase complex that mediates the stability regulatory protein 2, important posttranscriptional regulator several genes involved metabolism. The regulated iron- oxygen-responsive manner, contingent upon presence its N-terminal domain. Here we present atomic structure N terminus, hemerythrin-like α-helical bundle fold not previously...
Targeted degradation of proteins through the ubiquitin-proteasome system (UPS) via activities E3 ubiquitin ligases regulates diverse cellular processes, and misregulation these enzymes contributes to pathogenesis human diseases. One challenges facing UPS field is delineate complete cohort substrates for a particular ligase. Advances in mass spectrometry development antibodies recognizing Lys-ϵ-Gly-Gly (diGly) remnant from ubiquitinated following trypsinolysis have provided tool address this...
Iron regulatory proteins play a principal role in maintaining cellular iron homeostasis by post-transcriptionally regulating factors responsible for uptake, utilization, and storage. An E3 ubiquitin ligase complex containing FBXL5 targets IRP2 proteasomal degradation under iron- oxygen-replete conditions, whereas itself is degraded when oxygen availability decreases. contains hemerythrin-like (Hr) domain at its N terminus that mediates own differential stability. Here, we investigated the...
There is a growing interest in using targeted protein degradation as therapeutic modality view of its potential to expand the druggable proteome. One avenue this via molecular glue based Cereblon E3 Ligase Modulating Drug compounds. Here, we report identification transcription factor ZBTB16 neosubstrate. We also two new modulators, CC-3060 and CC-647, that promote degradation. Unexpectedly, CC-647 target for by primarily engaging distinct structural degrons on different zinc finger domains....
Thalidomide has a dark history as teratogen, but in recent years, its derivates have been shown to function potent chemotherapeutic agents. These drugs bind cereblon (CRBN), the substrate receptor of an E3 ubiquitin ligase complex, and modify degradation targets. Despite these insights, remarkably little is known about normal development. Here, we employ Ciona , simple invertebrate chordate, identify endogenous Crbn In Ciona, specifically expressed developing muscles during tail elongation...