ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress

Suguru Yamaguchi; Hisamitsu Ishihara; Takahiro Yamada; Akira Tamura; Masahiro Usui; Ryu Tominaga; Yuichiro Munakata; Chihiro Satake; Hideki Katagiri; Fumi Tashiro; Hiroyuki Aburatani; Kyoko Tsukiyama-Kohara; Jun ichi Miyazaki; Nahum Sonenberg; Yoshitomo Oka

doi:10.1016/j.cmet.2008.01.008

ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress

Suguru Yamaguchi, Hisamitsu Ishihara, Takahiro Yamada, Akira Tamura, Masahiro Usui, Ryu Tominaga, Yuichiro Munakata, Chihiro Satake, Hideki Katagiri, Fumi Tashiro, Hiroyuki Aburatani, Kyoko Tsukiyama-Kohara, Jun ichi Miyazaki, Nahum Sonenberg, Yoshitomo Oka

MED - Medical Sciences

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

151 Citations (Scopus)

Abstract

Endoplasmic reticulum (ER) stress-mediated apoptosis may play a crucial role in loss of pancreatic β cell mass, contributing to the development of diabetes. Here we show that induction of 4E-BP1, the suppressor of the mRNA 5′ cap-binding protein eukaryotic initiation factor 4E (eIF4E), is involved in β cell survival under ER stress. 4E-BP1 expression was increased in islets under ER stress in several mouse models of diabetes. The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4. Deletion of the Eif4ebp1 gene increased susceptibility to ER stress-mediated apoptosis in MIN6 β cells and mouse islets, which was accompanied by deregulated translational control. Furthermore, Eif4ebp1 deletion accelerated β cell loss and exacerbated hyperglycemia in mouse models of diabetes. Thus, 4E-BP1 induction contributes to the maintenance of β cell homeostasis during ER stress and is a potential therapeutic target for diabetes.

Original language	English
Pages (from-to)	269-276
Number of pages	8
Journal	Cell Metabolism
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2008.01.008
Publication status	Published - 2008 Mar 5

Keywords

HUMDISEASE
PROTEINS
SIGNALING

UN SDGs

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

Access to Document

10.1016/j.cmet.2008.01.008

Cite this

Yamaguchi, S., Ishihara, H., Yamada, T., Tamura, A., Usui, M., Tominaga, R., Munakata, Y., Satake, C., Katagiri, H., Tashiro, F., Aburatani, H., Tsukiyama-Kohara, K., Miyazaki, J. I., Sonenberg, N., & Oka, Y. (2008). ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress. Cell Metabolism, 7(3), 269-276. https://doi.org/10.1016/j.cmet.2008.01.008

@article{ce7c4396a3b64475ac6fb4af3fab63bb,

title = "ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress",

abstract = "Endoplasmic reticulum (ER) stress-mediated apoptosis may play a crucial role in loss of pancreatic β cell mass, contributing to the development of diabetes. Here we show that induction of 4E-BP1, the suppressor of the mRNA 5′ cap-binding protein eukaryotic initiation factor 4E (eIF4E), is involved in β cell survival under ER stress. 4E-BP1 expression was increased in islets under ER stress in several mouse models of diabetes. The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4. Deletion of the Eif4ebp1 gene increased susceptibility to ER stress-mediated apoptosis in MIN6 β cells and mouse islets, which was accompanied by deregulated translational control. Furthermore, Eif4ebp1 deletion accelerated β cell loss and exacerbated hyperglycemia in mouse models of diabetes. Thus, 4E-BP1 induction contributes to the maintenance of β cell homeostasis during ER stress and is a potential therapeutic target for diabetes.",

keywords = "HUMDISEASE, PROTEINS, SIGNALING",

author = "Suguru Yamaguchi and Hisamitsu Ishihara and Takahiro Yamada and Akira Tamura and Masahiro Usui and Ryu Tominaga and Yuichiro Munakata and Chihiro Satake and Hideki Katagiri and Fumi Tashiro and Hiroyuki Aburatani and Kyoko Tsukiyama-Kohara and Miyazaki, {Jun ichi} and Nahum Sonenberg and Yoshitomo Oka",

note = "Funding Information: We thank J. Alam (Alton Ochsner Medical Foundation) and D. Ron (New York University) for their generous gifts of DN-ATF4 cDNA and Atf4 −/− MEFs, respectively. We are also grateful to K. Igarashi (Tohoku University) for advice on ChIP analysis and to Y. Nagura and K. Tanaka for their expert technical assistance. This work was supported by Grants-in-Aid for Scientific Research (19590300 to H.I. and 19209034 to Y.O.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. ",

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Yamaguchi, S, Ishihara, H, Yamada, T, Tamura, A, Usui, M, Tominaga, R, Munakata, Y, Satake, C, Katagiri, H, Tashiro, F, Aburatani, H, Tsukiyama-Kohara, K, Miyazaki, JI, Sonenberg, N & Oka, Y 2008, 'ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress', Cell Metabolism, vol. 7, no. 3, pp. 269-276. https://doi.org/10.1016/j.cmet.2008.01.008

TY - JOUR

T1 - ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress

AU - Yamaguchi, Suguru

AU - Ishihara, Hisamitsu

AU - Yamada, Takahiro

AU - Tamura, Akira

AU - Usui, Masahiro

AU - Tominaga, Ryu

AU - Munakata, Yuichiro

AU - Satake, Chihiro

AU - Katagiri, Hideki

AU - Tashiro, Fumi

AU - Aburatani, Hiroyuki

AU - Tsukiyama-Kohara, Kyoko

AU - Miyazaki, Jun ichi

AU - Sonenberg, Nahum

AU - Oka, Yoshitomo

N1 - Funding Information: We thank J. Alam (Alton Ochsner Medical Foundation) and D. Ron (New York University) for their generous gifts of DN-ATF4 cDNA and Atf4 −/− MEFs, respectively. We are also grateful to K. Igarashi (Tohoku University) for advice on ChIP analysis and to Y. Nagura and K. Tanaka for their expert technical assistance. This work was supported by Grants-in-Aid for Scientific Research (19590300 to H.I. and 19209034 to Y.O.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

PY - 2008/3/5

Y1 - 2008/3/5

N2 - Endoplasmic reticulum (ER) stress-mediated apoptosis may play a crucial role in loss of pancreatic β cell mass, contributing to the development of diabetes. Here we show that induction of 4E-BP1, the suppressor of the mRNA 5′ cap-binding protein eukaryotic initiation factor 4E (eIF4E), is involved in β cell survival under ER stress. 4E-BP1 expression was increased in islets under ER stress in several mouse models of diabetes. The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4. Deletion of the Eif4ebp1 gene increased susceptibility to ER stress-mediated apoptosis in MIN6 β cells and mouse islets, which was accompanied by deregulated translational control. Furthermore, Eif4ebp1 deletion accelerated β cell loss and exacerbated hyperglycemia in mouse models of diabetes. Thus, 4E-BP1 induction contributes to the maintenance of β cell homeostasis during ER stress and is a potential therapeutic target for diabetes.

AB - Endoplasmic reticulum (ER) stress-mediated apoptosis may play a crucial role in loss of pancreatic β cell mass, contributing to the development of diabetes. Here we show that induction of 4E-BP1, the suppressor of the mRNA 5′ cap-binding protein eukaryotic initiation factor 4E (eIF4E), is involved in β cell survival under ER stress. 4E-BP1 expression was increased in islets under ER stress in several mouse models of diabetes. The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4. Deletion of the Eif4ebp1 gene increased susceptibility to ER stress-mediated apoptosis in MIN6 β cells and mouse islets, which was accompanied by deregulated translational control. Furthermore, Eif4ebp1 deletion accelerated β cell loss and exacerbated hyperglycemia in mouse models of diabetes. Thus, 4E-BP1 induction contributes to the maintenance of β cell homeostasis during ER stress and is a potential therapeutic target for diabetes.

KW - HUMDISEASE

KW - PROTEINS

KW - SIGNALING

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