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Publication : NeuCode Proteomics Reveals Bap1 Regulation of Metabolism.

First Author  Baughman JM Year  2016
Journal  Cell Rep Volume  16
Issue  2 Pages  583-95
PubMed ID  27373151 Mgi Jnum  J:238588
Mgi Id  MGI:5823122 Doi  10.1016/j.celrep.2016.05.096
Citation  Baughman JM, et al. (2016) NeuCode Proteomics Reveals Bap1 Regulation of Metabolism. Cell Rep 16(2):583-95
abstractText  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.
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