NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

被引：61

作者：

Baughman, Joshua M. ^{[1
]}

Rose, Christopher M. ^{[10
]}

Kolumam, Ganesh ^{[2
]}

Webster, Joshua D. ^{[3
]}

Wilkerson, Emily M. ^{[10
]}

Merrill, Anna E. ^{[10
]}

Rhoads, Timothy W. ^{[13
]}

Noubade, Rajkumar ^{[4
]}

Katavolos, Paula ^{[5
]}

Lesch, Justin ^{[6
]}

Stapleton, Donald S. ^{[11
]}

Rabaglia, Mary E. ^{[11
]}

Schueler, Kathy L. ^{[11
]}

Asuncion, Raymond ^{[7
]}

Domeyer, Melanie ^{[7
]}

Zavala-Solorio, Jose ^{[2
]}

Reich, Michael ^{[8
]}

DeVoss, Jason ^{[6
]}

Keller, Mark P. ^{[11
]}

Attie, Alan D. ^{[11
]}

Hebert, Alexander S. ^{[13
]}

Westphall, Michael S. ^{[13
]}

Coon, Joshua J. ^{[10
,12
,13
]}

Kirkpatrick, Donald S. ^{[1
]}

Dey, Anwesha ^{[9
]}

机构：

[1] Genentech Inc, Dept Prot Chem, 1 DNA Way, San Francisco, CA 94080 USA

[2] Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA

[3] Genentech Inc, Dept Pathol, 1 DNA Way, San Francisco, CA 94080 USA

[4] Genentech Inc, Dept Immunol, 1 DNA Way, San Francisco, CA 94080 USA

[5] Genentech Inc, Dept Safety Assessment, 1 DNA Way, San Francisco, CA 94080 USA

[6] Genentech Inc, Dept Translat Immunol, 1 DNA Way, San Francisco, CA 94080 USA

[7] Genentech Inc, Dept Transgen Technol, 1 DNA Way, San Francisco, CA 94080 USA

[8] Genentech Inc, Dept Lab Anim Resources, 1 DNA Way, San Francisco, CA 94080 USA

[9] Genentech Inc, Dept Discovery Oncol, 1 DNA Way, San Francisco, CA 94080 USA

[10] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

[11] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

[12] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA

[13] Univ Wisconsin, Genome Ctr Wisconsin, Madison, WI 53706 USA

来源：

CELL REPORTS | 2016年 / 16卷 / 02期

关键词：

ACTIVATED RECEPTOR-GAMMA; ENCODED MASS SIGNATURES; IN-VIVO; RECIPROCAL REGULATION; SILAC MOUSE; O-GLCNAC; MICE; COMPLEX; CANCER; GENE;

D O I：

10.1016/j.celrep.2016.05.096

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：583 / 595

页数：13

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