Article
Cell Biology
Hyeon-Ok Jin, Sung-Eun Hong, Ji-Young Kim, Se-Kyeong Jang, In-Chul Park
Summary: Amino acid deprivation induces the activation of GCN2/ATF4/REDD1 axis, leading to AKT activation and promoting the survival signal in cancer cells. REDD1 plays a crucial role in the response of cells to amino acid deprivation and radiotherapy.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Se-Kyeong Jang, Sung-Eun Hong, Da-Hee Lee, Ji-Young Kim, Ji Yea Kim, Sang-Kyu Ye, Jungil Hong, In-Chul Park, Hyeon-Ok Jin
Summary: Metformin inhibits mTORC1 activity by inducing the expression of ATF4, REDD1, and Sestrin2 independently of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, while knockdown of REDD1 and Sestrin2 reduces sensitivity to both metformin and lapatinib. These findings suggest a potential therapeutic value of the ATF4-induced REDD1 and Sestrin2 signaling pathway in mTORC1 inhibition.
Article
Endocrinology & Metabolism
Lin Mu, Nan Chen, Yakun Chen, Zhifen Yang, Huandi Zhou, Shan Song, Yonghong Shi
Summary: This study found that REDD1 was elevated in DN patients and diabetic mice, and REDD1 deficiency significantly improved apoptosis and EMT in DN mice. It was also discovered that inhibiting REDD1 could suppress the synthesis of Nox4 and ROS induced by HG.
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ekaterina M. Zhidkova, Evgeniya S. Lylova, Diana D. Grigoreva, Kirin Kirsanov, Alena Osipova, Evgeny P. Kulikov, Sergey A. Mertsalov, Gennady A. Belitsky, Irina Budunova, Marianna G. Yakubovskaya, Ekaterina A. Lesovaya
Summary: REDD1, as an immediate early response gene, is activated by various stress conditions and involved in the regulation of cell signaling and processes. It inhibits proliferative signaling and regulates metabolism by repression of mTOR, and is implicated in diseases such as cancer and inflammation. Recent studies also revealed its involvement in the adverse atrophogenic effects induced by glucocorticoids, providing insights into safer glucocorticoid receptor-targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Abigail S. Krall, Peter J. Mullen, Felicia Surjono, Milica Momcilovic, Ernst W. Schmid, Christopher J. Halbrook, Apisadaporn Thambundit, Steven D. Mittelman, Costas A. Lyssiotis, David B. Shackelford, Simon R. Knott, Heather R. Christofk
Summary: Mitochondrial respiration is essential for cell proliferation by generating biosynthetic precursors like aspartate. Inhibition of electron transport chain can deplete aspartate and impair ATF4 and mTORC1 activities. Adding exogenous asparagine can restore these activities and promote cell proliferation in the context of ETC inhibition.
Article
Multidisciplinary Sciences
Dong-Keon Lee, Taesam Kim, Junyoung Byeon, Minsik Park, Suji Kim, Joohwan Kim, Seunghwan Choi, Gihwan Lee, Chanin Park, Keun Woo Lee, Yong Jung Kwon, Jeong-Hyung Lee, Young-Guen Kwon, Young-Myeong Kim
Summary: The REDD1-NF-kappa B axis plays a crucial role in metabolic inflammation and dysregulation, with Redd1 deficiency inhibiting diet-induced obesity, inflammation, insulin resistance, and hepatic steatosis.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Salida Mirzoeva, Yuchen Yang, Anna Klopot, Irina Budunova, Melissa A. Brown
Summary: REDD1 is an essential immune modulator that influences the initiation and effector phase of ACD disease by driving naive T cell activation and promoting immune cell trafficking in T cell-mediated skin inflammation.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Cell Biology
Leticia Perez-Sisques, Anna Sancho-Balsells, Julia Solana-Balaguer, Genis Campoy-Campos, Marcel Vives-Isern, Ferran Soler-Palazon, Marta Anglada-Huguet, Miguel-Angel Lopez-Toledano, Eva-Maria Mandelkow, Jordi Alberch, Albert Giralt, Cristina Malagelada
Summary: RTP801 protein levels are increased in postmortem hippocampal samples from AD patients, correlating with disease progression and GFAP expression. Downregulation of RTP801 in mouse models improves cognitive deficits and reverses gliosis hallmarks and inflammasome proteins. This suggests that RTP801 could be a potential future therapeutic target for AD, serving as a biomarker of neuroinflammation severity and a promising target for treatment.
CELL DEATH & DISEASE
(2021)
Article
Endocrinology & Metabolism
Siddharth Sunilkumar, Esma I. Yerlikaya, Allyson L. Toro, William P. Miller, Han Chen, Kebin Hu, Scot R. Kimball, Michael D. Dennis
Summary: Chronic hyperglycemia promotes the expression of REDD1 in the kidney, leading to oxidative stress and renal injury. Deletion of REDD1 reduces reactive oxygen species and prevents podocyte loss, indicating its role in diabetes-induced renal complications.
Article
Endocrinology & Metabolism
Shaunaci A. Stevens, Maria K. Gonzalez Aguiar, Allyson L. Toro, Esma I. Yerlikaya, Siddharth Sunilkumar, Ashley M. VanCleave, Jessica Pfleger, Elisa A. Bradley, Scot R. Kimball, Michael D. Dennis
Summary: The interplay between endoplasmic reticulum stress and inflammation contributes to cardiovascular disease progression. This study identifies REDD1, a stress response protein, as a missing link that connects the development of endoplasmic reticulum stress with increased production of proinflammatory cytokines in the hearts of obese mice.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Endocrinology & Metabolism
William P. Miller, Allyson L. Toro, Siddharth Sunilkumar, Shaunaci A. Stevens, Ashley M. VanCleave, David L. Williamson, Alistair J. Barber, Michael D. Dennis
Summary: Clinical studies support the role of REDD1 protein in ischemic retinal complications caused by diabetes. The study found that REDD1 expression specifically in Muller glia contributes to diabetes-induced retinal pathology, including gliosis, neurodegeneration, and impaired vision.
Article
Biochemistry & Molecular Biology
Robert P. Feehan, Catherine S. Coleman, Shauna Ebanks, Charles H. Lang, Lisa M. Shantz
Summary: This study aims to investigate the role of REDD1 in the UVB stress response, demonstrating that REDD1 knockout sensitizes keratinocytes to UVB-induced apoptosis and intensifies mitochondrial ROS generation. Furthermore, it was found that REDD1 interacts with AIF and the mitochondrial import protein CHCHD4, highlighting the importance of REDD1 in protecting cells from UVB-induced ROS toxicity as part of a mitochondrial complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Food Science & Technology
Jie Yang, Shibo Bao, Shengxiang Luo, Liping Jiang, Qiujuan Li, Ying Kong, Jun Cao, Jun Cao
Summary: Curcumin inhibits both autophagy and the mTOR pathway, and they both play a significant role in suppressing the growth of A549 cells. Blocking ATF4 reduces the expression of autophagy-related proteins and AKT/mTOR. Curcumin can effectively reduce the weight and volume of transplanted tumors in mice.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Zhenzhen Liu, Wenting Leng, Jianmin Zhang, Guangru Zhang, Disheng Liu, Zhiyu Zhao, Feng Chen, Yajing Shi, Yingxiang Hao, Jipeng Lv, Zhanhai Wan, Yan Zhang, Xin Liu, Yongqiang Liu, Yufang Leng
Summary: This study highlights the role of miR-146a-5p in regulating autophagy by targeting TXNIP and suggests that miR-146a-5p may be a novel drug target for intestinal I/R therapy.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Cell Biology
Marta Montori-Grau, David Aguilar-Recarte, Mohammad Zarei, Javier Pizarro-Delgado, Xavier Palomer, Manuel Vazquez-Carrera
Summary: This study found that endoplasmic reticulum (ER) stress downregulates the expression of PGC-1 alpha in skeletal muscle through the activation of ATF4 and the mTOR-CRTC2 pathway. These findings suggest that inhibition of ATF4 and the mTOR-CRTC2 axis could be a therapeutic target for insulin resistant states.
CELL COMMUNICATION AND SIGNALING
(2022)