Journal article
NeuCode Proteomics Reveals Bap1 Regulation of Metabolism
Cell reports (Cambridge), Vol.16(2), pp.583-595
07/12/2016
DOI: 10.1016/j.celrep.2016.05.096
PMCID: PMC5546211
PMID: 27373151
Abstract
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.
Details
- Title: Subtitle
- NeuCode Proteomics Reveals Bap1 Regulation of Metabolism
- Creators
- Joshua M Baughman - GenentechChristopher M Rose - University of Wisconsin–MadisonGanesh Kolumam - GenentechJoshua D Webster - GenentechEmily M Wilkerson - University of Wisconsin–MadisonAnna E Merrill - University of Wisconsin–MadisonTimothy W Rhoads - University of Wisconsin–MadisonRajkumar Noubade - GenentechPaula Katavolos - GenentechJustin Lesch - GenentechDonald S Stapleton - University of Wisconsin–MadisonMary E Rabaglia - University of Wisconsin–MadisonKathy L Schueler - University of Wisconsin–MadisonRaymond Asuncion - GenentechMelanie Domeyer - GenentechJose Zavala-Solorio - Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USAMichael Reich - GenentechJason DeVoss - GenentechMark P Keller - University of Wisconsin–MadisonAlan D Attie - University of Wisconsin–MadisonAlexander S Hebert - University of Wisconsin–MadisonMichael S Westphall - University of Wisconsin–MadisonJoshua J Coon - University of Wisconsin–MadisonDonald S Kirkpatrick - GenentechAnwesha Dey - Genentech
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.16(2), pp.583-595
- DOI
- 10.1016/j.celrep.2016.05.096
- PMID
- 27373151
- PMCID
- PMC5546211
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- T32 HL007899 / NHLBI NIH HHS P41 GM108538 / NIGMS NIH HHS T32 HG002760 / NHGRI NIH HHS R01 DK066369 / NIDDK NIH HHS T32 GM008505 / NIGMS NIH HHS T15 LM007359 / NLM NIH HHS R01 DK101573 / NIDDK NIH HHS R01 GM080148 / NIGMS NIH HHS
- Language
- English
- Date published
- 07/12/2016
- Academic Unit
- Pathology; Injury Prevention Research Center
- Record Identifier
- 9984186547102771
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