NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

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

doi:10.1016/j.celrep.2016.05.096

NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

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

Department of Cell Biology & Physiology

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

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.

Original language	English
Pages (from-to)	583-595
Number of pages	13
Journal	Cell Reports
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2016.05.096
State	Published - Jul 12 2016

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Baughman, J. M., Rose, C. M., Kolumam, G., Webster, J. D., Wilkerson, E. M., Merrill, A. E., Rhoads, T. W., Noubade, R., Katavolos, P., Lesch, J., Stapleton, D. S., Rabaglia, M. E., Schueler, K. L., Asuncion, R., Domeyer, M., Zavala-Solorio, J., Reich, M., DeVoss, J., Keller, M. P., ... Dey, A. (2016). NeuCode Proteomics Reveals Bap1 Regulation of Metabolism. Cell Reports, 16(2), 583-595. https://doi.org/10.1016/j.celrep.2016.05.096

@article{86490a2efdaf454b966e595849e1d3e2,

title = "NeuCode Proteomics Reveals Bap1 Regulation of Metabolism",

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.",

author = "Baughman, {Joshua M.} and Rose, {Christopher M.} and Ganesh Kolumam and Webster, {Joshua D.} and Wilkerson, {Emily M.} and Merrill, {Anna E.} and Rhoads, {Timothy W.} and Rajkumar Noubade and Paula Katavolos and Justin Lesch and Stapleton, {Donald S.} and Rabaglia, {Mary E.} and Schueler, {Kathy L.} and Raymond Asuncion and Melanie Domeyer and Jose Zavala-Solorio and Michael Reich and Jason DeVoss and Keller, {Mark P.} and Attie, {Alan D.} and Hebert, {Alexander S.} and Westphall, {Michael S.} and Coon, {Joshua J.} and Kirkpatrick, {Donald S.} and Anwesha Dey",

note = "Publisher Copyright: {\textcopyright} 2016",

year = "2016",

month = jul,

day = "12",

doi = "10.1016/j.celrep.2016.05.096",

language = "English",

volume = "16",

pages = "583--595",

journal = "Cell Reports",

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Baughman, JM, Rose, CM, Kolumam, G, Webster, JD, Wilkerson, EM, Merrill, AE, Rhoads, TW, Noubade, R, Katavolos, P, Lesch, J, Stapleton, DS, Rabaglia, ME, Schueler, KL, Asuncion, R, Domeyer, M, Zavala-Solorio, J, Reich, M, DeVoss, J, Keller, MP, Attie, AD, Hebert, AS, Westphall, MS, Coon, JJ, Kirkpatrick, DS & Dey, A 2016, 'NeuCode Proteomics Reveals Bap1 Regulation of Metabolism', Cell Reports, vol. 16, no. 2, pp. 583-595. https://doi.org/10.1016/j.celrep.2016.05.096

TY - JOUR

T1 - NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

AU - Baughman, Joshua M.

AU - Rose, Christopher M.

AU - Kolumam, Ganesh

AU - Webster, Joshua D.

AU - Wilkerson, Emily M.

AU - Merrill, Anna E.

AU - Rhoads, Timothy W.

AU - Noubade, Rajkumar

AU - Katavolos, Paula

AU - Lesch, Justin

AU - Stapleton, Donald S.

AU - Rabaglia, Mary E.

AU - Schueler, Kathy L.

AU - Asuncion, Raymond

AU - Domeyer, Melanie

AU - Zavala-Solorio, Jose

AU - Reich, Michael

AU - DeVoss, Jason

AU - Keller, Mark P.

AU - Attie, Alan D.

AU - Hebert, Alexander S.

AU - Westphall, Michael S.

AU - Coon, Joshua J.

AU - Kirkpatrick, Donald S.

AU - Dey, Anwesha

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84978532196&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.05.096

DO - 10.1016/j.celrep.2016.05.096

M3 - Article

C2 - 27373151

AN - SCOPUS:84978532196

SN - 2639-1856

VL - 16

SP - 583

EP - 595

JO - Cell Reports

JF - Cell Reports

IS - 2

ER -

NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

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