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NeuCode Proteomics Reveals Bap1 Regulation of Metabolism.
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.
Affiliation
  • Baughman JM; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Rose CM; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Kolumam G; Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Webster JD; Department of Pathology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Wilkerson EM; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Merrill AE; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Rhoads TW; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Noubade R; Department of Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Katavolos P; Department of Safety Assessment, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Lesch J; Department of Translational Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Stapleton DS; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Rabaglia ME; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Schueler KL; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Asuncion R; Department of Transgenic Technology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Domeyer M; Department of Transgenic Technology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Zavala-Solorio J; Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Reich M; Department of Laboratory Animal Resources, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • DeVoss J; Department of Translational Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
  • Keller MP; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Attie AD; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Hebert AS; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Westphall MS; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Coon JJ; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: jcoon@chem.wisc.ed
  • Kirkpatrick DS; Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: kirkpatrick.donald@gene.com.
  • Dey A; Department of Discovery Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: dey.anwesha@gene.com.
Cell Rep ; 16(2): 583-595, 2016 07 12.
Article in En | MEDLINE | ID: mdl-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Suppressor Proteins / Proteomics / Ubiquitin Thiolesterase Limits: Animals Language: En Journal: Cell Rep Year: 2016 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Suppressor Proteins / Proteomics / Ubiquitin Thiolesterase Limits: Animals Language: En Journal: Cell Rep Year: 2016 Document type: Article Affiliation country: Estados Unidos