Brap regulates liver morphology and hepatocyte turnover via modulation of the Hippo pathway

Abstract

Significance The liver has a complex cellular architecture that is essential for its function. In this work, we show that BRAP, a ubiquitin ligase of poorly understood function, is required for maintenance of proper liver morphology. BRAP deletion in the liver causes disruption of its normal architecture and inflammation due to altered expression of genes involved in cell growth and extracellular interactions. This work sheds light on the mechanisms that maintain proper liver structure and has implications for liver disease.

Small Molecule Screen Identifies Non-catalytic USP3 Chemical Handle

“…While our docked model of 59 (Figure ) and previously published ligands targeting other ZnF-UBD proteins − (Figure ) indicate that the carboxylic moiety of the compound is deeply buried in the binding pocket, the pyrrolopyridine ring is predicted to be partially solvent exposed and may serve as an anchor point for linker attachment for the development of proximity pharmacology agents. In addition to 59 , the focused chemical library screen also identified hits against other ZnF-UBDs, such as USP16 and BRAP ( 50 and 46 , respectively) which require further validation, but may be promising starting points for hit expansion for these other disease-relevant protein targets. , …”

“…In addition to 59, the focused chemical library screen also identified hits against other ZnF-UBDs, such as USP16 and BRAP (50 and 46, respectively) which require further validation, but may be promising starting points for hit expansion for these other disease-relevant protein targets. 34,35 ■ MATERIALS AND METHODS Cloning, Protein Expression, and Purification. cDNAs encoding Ub 1−76 , Ub 1−73 , USP5 171−290 , and HDAC6 1109−1215 were cloned as previously described.…”

Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs

“…Frozen liver samples were prepared as described previously ( Priest et al 2022 ) by precipitating proteins. A glycogen assay kit (Sigma-Aldrich) was used according to the manufacturer's instructions, and the measurements were normalized to protein content.…”

“…Proteins were isolated with radioimmunoprecipitation assay buffer (Boston BioProducts) as described previously ( Priest et al 2022 ). Samples were loaded onto Bis-Tris gels, and proteins were separated by electrophoresis and then transferred to polyvinylidene difluoride membranes.…”