NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

作者：Baughman Joshua M; Rose Christopher M; Kolumam Ganesh; Webster Joshua D; Wilkerson Emily M; Merrill Anna E; Rhoads Timothy W; Noubade Rajkumar; Katavolos Paula; Lesch Justin; Stapleton Donald S; Rabaglia Mary E; Schueler Kathy L; Asuncion Raymond; Domeyer Melanie; Zavala Solorio Jose; Reich Michael; DeVoss Jason; Keller Mark P; Attie Alan D; Hebert Alexander S; Westphall Michael S; Coon Joshua J^*; Kirkpatrick Donald S^*; Dey Anwesha^*

来源：Cell Reports, 2016, 16(2): 583-595.

DOI：10.1016/j.celrep.2016.05.096

We introduce neutron-encoded (NeuCode) amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

• 出版日期2016-7-12