Jagn1 Is Induced in Response to ER Stress and Regulates Proinsulin Biosynthesis

被引：9

作者：

Nosak, Courtney ^{[1
]}

Silva, Pamuditha N. ^{[2
]}

Sollazzo, Pietro ^{[3
]}

Moon, Kyung-Mee ^{[4
,5
]}

Odisho, Tanya ^{[1
]}

Foster, Leonard J. ^{[4
,5
]}

Rocheleau, Jonathan V. ^{[1
,2
]}

Volchuk, Allen ^{[6
]}

机构：

[1] Univ Toronto, Dept Physiol, Toronto, ON, Canada

[2] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada

[3] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[4] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada

[5] Univ British Columbia, Ctr High Throughput Biol, Vancouver, BC V5Z 1M9, Canada

[6] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, 30 Bond St, Toronto, ON M5B 1W8, Canada

来源：

PLOS ONE | 2016年 / 11卷 / 02期

基金：

加拿大自然科学与工程研究理事会;

关键词：

ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; CELL-LINES; INFLAMMATION; DEFICIENCY; GOLGI;

D O I：

10.1371/journal.pone.0149177

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Jagn1 protein was indentified in a SILAC proteomic screen of proteins that are increased in insulinoma cells expressing a folding-deficient proinsulin. Jagn1 mRNA was detected in primary rodent islets and in insulinoma cell lines and the levels were increased in response to ER stress. The function of Jagn1 was assessed in insulinoma cells by both knock-down and overexpression approaches. Knock-down of Jagn1 caused an increase in glucose-stimulated insulin secretion resulting from an increase in proinsulin biosynthesis. In contrast, overexpression of Jagn1 in insulinoma cells resulted in reduced cellular proinsulin and insulin levels. Our results identify a novel role for Jagn1 in regulating proinsulin biosynthesis in pancreatic beta-cells. Under ER stress conditions Jagn1 is induced which might contribute to reducing proinsulin biosynthesis, in part by helping to relieve the protein folding load in the ER in an effort to restore ER homeostasis.

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页数：14

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共 20 条

[1] ESTABLISHMENT OF 2-MERCAPTOETHANOL-DEPENDENT DIFFERENTIATED INSULIN-SECRETING CELL-LINES [J].

ASFARI, M ;

JANJIC, D ;

MEDA, P ;

LI, GD ;

HALBAN, PA ;

WOLLHEIM, CB .

ENDOCRINOLOGY, 1992, 130 (01) :167-178

[2] Quantitative Mass Spectrometry Catalogues Salmonella Pathogenicity Island-2 Effectors and Identifies Their Cognate Host Binding Partners [J].

Auweter, Sigrid D. ;

Bhavsar, Amit P. ;

de Hoog, Carmen L. ;

Li, Yuling ;

Chan, Y. Alina ;

van der Heijden, Joris ;

Lowden, Michael J. ;

Coombes, Brian K. ;

Rogers, Lindsay D. ;

Stoynov, Nikolay ;

Foster, Leonard J. ;

Finlay, B. Brett .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (27) :24023-24035

[3] Ribosomal Protein L13a Deficiency in Macrophages Promotes Atherosclerosis by Limiting Translation Control-Dependent Retardation of Inflammation [J].

Basu, Abhijit ;

Poddar, Darshana ;

Robinet, Peggy ;

Smith, Jonathan D. ;

Febbraio, Maria ;

Baldwin, William M., III ;

Mazumder, Barsanjit .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2014, 34 (03) :533-542

[4] JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia [J].

Boztug, Kaan ;

Jaervinen, Paeivi M. ;

Salzer, Elisabeth ;

Racek, Tomas ;

Moench, Sebastian ;

Garncarz, Wojciech ;

Gertz, E. Michael ;

Schaeffer, Alejandro A. ;

Antonopoulos, Aristotelis ;

Haslam, Stuart M. ;

Schieck, Lena ;

Puchalka, Jacek ;

Diestelhorst, Jana ;

Appaswamy, Giridharan ;

Lescoeur, Brigitte ;

Giambruno, Roberto ;

Bigenzahn, Johannes W. ;

Elling, Ulrich ;

Pfeifer, Dietmar ;

Conde, Cecilia Dominguez ;

Albert, Michael H. ;

Welte, Karl ;

Brandes, Gudrun ;

Sherkat, Roya ;

ten Bosch, Jutte van der Werff ;

Rezaei, Nima ;

Etzioni, Amos ;

Bellanne-Chantelot, Christine ;

Superti-Furga, Giulio ;

Penninger, Josef M. ;

Bennett, Keiryn L. ;

von Blume, Julia ;

Dell, Anne ;

Donadieu, Jean ;

Klein, Christoph .

NATURE GENETICS, 2014, 46 (09) :1021-+

[5] Organization of the ER-Golgi interface for membrane traffic control [J].

Brandizzi, Federica ;

Barlowe, Charles .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (06) :382-392

[6] Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation [J].

Eizirik, D. L. ;

Miani, M. ;

Cardozo, A. K. .

DIABETOLOGIA, 2013, 56 (02) :234-241

[7] The role for endoplasmic reticulum stress in diabetes mellitus [J].

Eizirik, Decio L. ;

Cardozo, Alessandra K. ;

Cnop, Miriam .

ENDOCRINE REVIEWS, 2008, 29 (01) :42-61

[8] Endoplasmic reticulum stress response in an INS-1 pancreatic β-cell line with inducible expression of a folding-deficient proinsulin [J].

Hartley, Taila ;

Siva, Madura ;

Lai, Elida ;

Teodoro, Tracy ;

Zhang, Liling ;

Volchuk, Allen .

BMC CELL BIOLOGY, 2010, 11

[9] Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion [J].

Hohmeier, HE ;

Mulder, H ;

Chen, GX ;

Henkel-Rieger, R ;

Prentki, M ;

Newgard, CB .

DIABETES, 2000, 49 (03) :424-430

[10] Bi-directional protein transport between the ER and Golgi [J].

Lee, MCS ;

Miller, EA ;

Goldberg, J ;

Orci, L ;

Schekman, R .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2004, 20 :87-123