Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes

Wendy M. McKimpson; Yun Chen; James A. Irving; Min Zheng; Jeremy Weinberger; Wilson Lek Wen Tan; Zenia Tiang; Alistair M. Jagger; Streamson C. Chua; Jeffrey E. Pessin; Roger S.Y. Foo; David A. Lomas; Richard N. Kitsis

doi:10.1016/j.devcel.2021.02.011

Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes

Wendy M. McKimpson, Yun Chen, James A. Irving, Min Zheng, Jeremy Weinberger, Wilson Lek Wen Tan, Zenia Tiang, Alistair M. Jagger, Streamson C. Chua, Jeffrey E. Pessin, Roger S.Y. Foo, David A. Lomas, Richard N. Kitsis

Medicine

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

5 Scopus citations

Abstract

While cytoplasmic ARC maintains survival of insulin-producing pancreatic β cells, McKimpson et al. show that a pool of ARC relocates to the nucleus during diabetes where it paradoxically triggers cell death. The mechanism involves downregulation of AAT expression and secretion unleashing elastase-dependent loss of β cell adhesion and cell death.

Original language	English (US)
Pages (from-to)	747-760.e6
Journal	Developmental cell
Volume	56
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2021.02.011
State	Published - Mar 22 2021

Keywords

ARC
alpha-1 antitrypsin
cell death
diabetes
serpins

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.devcel.2021.02.011

Cite this

McKimpson, W. M., Chen, Y., Irving, J. A., Zheng, M., Weinberger, J., Tan, W. L. W., Tiang, Z., Jagger, A. M., Chua, S. C., Pessin, J. E., Foo, R. S. Y., Lomas, D. A., & Kitsis, R. N. (2021). Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes. Developmental cell, 56(6), 747-760.e6. https://doi.org/10.1016/j.devcel.2021.02.011

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title = "Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes",

abstract = "While cytoplasmic ARC maintains survival of insulin-producing pancreatic β cells, McKimpson et al. show that a pool of ARC relocates to the nucleus during diabetes where it paradoxically triggers cell death. The mechanism involves downregulation of AAT expression and secretion unleashing elastase-dependent loss of β cell adhesion and cell death.",

keywords = "ARC, alpha-1 antitrypsin, cell death, diabetes, serpins",

author = "McKimpson, {Wendy M.} and Yun Chen and Irving, {James A.} and Min Zheng and Jeremy Weinberger and Tan, {Wilson Lek Wen} and Zenia Tiang and Jagger, {Alistair M.} and Chua, {Streamson C.} and Pessin, {Jeffrey E.} and Foo, {Roger S.Y.} and Lomas, {David A.} and Kitsis, {Richard N.}",

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doi = "10.1016/j.devcel.2021.02.011",

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T1 - Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes

AU - McKimpson, Wendy M.

AU - Chen, Yun

AU - Irving, James A.

AU - Zheng, Min

AU - Weinberger, Jeremy

AU - Tan, Wilson Lek Wen

AU - Tiang, Zenia

AU - Jagger, Alistair M.

AU - Chua, Streamson C.

AU - Pessin, Jeffrey E.

AU - Foo, Roger S.Y.

AU - Lomas, David A.

AU - Kitsis, Richard N.

PY - 2021/3/22

Y1 - 2021/3/22

N2 - While cytoplasmic ARC maintains survival of insulin-producing pancreatic β cells, McKimpson et al. show that a pool of ARC relocates to the nucleus during diabetes where it paradoxically triggers cell death. The mechanism involves downregulation of AAT expression and secretion unleashing elastase-dependent loss of β cell adhesion and cell death.

AB - While cytoplasmic ARC maintains survival of insulin-producing pancreatic β cells, McKimpson et al. show that a pool of ARC relocates to the nucleus during diabetes where it paradoxically triggers cell death. The mechanism involves downregulation of AAT expression and secretion unleashing elastase-dependent loss of β cell adhesion and cell death.

KW - ARC

KW - alpha-1 antitrypsin

KW - cell death

KW - diabetes

KW - serpins

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SN - 1534-5807

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JO - Developmental cell

JF - Developmental cell

IS - 6

ER -

Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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