Ask about this productRelated genes to: DDIT4L antibody
- Gene:
- DDIT4L NIH gene
- Name:
- DNA damage inducible transcript 4 like
- Previous symbol:
- -
- Synonyms:
- REDD2, Rtp801L
- Chromosome:
- 4q24
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-12
- Date modifiied:
- 2019-02-19
Related products to: DDIT4L antibody
Related articles to: DDIT4L antibody
- The stress response proteins regulated in development and DNA damage (REDD)1 and REDD2 act as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1). While the role of REDD1 in diabetes complications in the retina has been well-explored, the potential contribution of REDD2 has not been previously examined. In mice fed a pro-diabetogenic high-fat diet, REDD2 mRNA ribosome-association was increased in retinal Müller glia. Hyperlipidemic culture conditions also increased both REDD1 and REDD2 mRNA expression in human Müller cell cultures. Mechanistic studies identified key regulatory residues in REDD2 at P100 and K179/Y182 that were necessary for mTORC1 suppression. In Müller cells exposed to hyperlipidemic conditions, REDD1 and REDD2 mRNA expression were upregulated in coordination with markers of ER stress. However, chemical induction of ER stress with tunicamycin increased REDD1, but not REDD2. Rather, increased REDD2 mRNA expression in Müller cells exposed to hyperlipidemic conditions required the transcription factors p53 and nuclear factor erythroid 2-related factor 2 (Nrf2). Unlike the Nrf2-target heme oxygenase 1 (HO-1), the effect of Nrf2 on REDD2 was redox-independent, as REDD2 expression was insensitive to the antioxidant N-acetylcysteine, the Nrf2 agonist sulforaphane, or oxidant stress. Hyperlipidemic conditions attenuated the inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β) and GSK3β inhibition suppressed REDD2 mRNA expression under hyperlipidemic conditions. Expression of a constitutively active GSK3β variant also promoted REDD2 mRNA expression in a manner that required both p53 and Nrf2. The findings support that GSK3β promotes REDD2 mRNA transcription in Müller glia under hyperlipidemic conditions via activation of p53/Nrf2. - Source: PubMed
Publication date: 2026/03/07
VanCleave Ashley MSunilkumar SiddharthToro Allyson LKimball Scot RDennis Michael D - The stress response proteins regulated in development and DNA damage (REDD)1 and REDD2 act as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1). Prior studies support that REDD1 is rapidly degraded via both chaperone-mediated autophagy (CMA) and the ubiquitin proteasome system (UPS). Compared to REDD1, relatively little is known regarding the regulation of REDD2. The objective here was to investigate the molecular mechanisms that control the cellular abundance of REDD2. Genetic and pharmacologic interventions were used to manipulate protein synthesis and proteolysis. We found that both REDD1 and REDD2 were rapidly degraded with half-lives of <20 min. Interestingly, REDD2 expression reduced the rate of REDD1 degradation, suggesting that the molecular mechanism through which they are degraded overlaps. However, in contrast with REDD1, CMA activation did not promote REDD2 degradation, despite the conservation of a putative KFERQ-like motif sequence in REDD2. Instead, we provide evidence that the rapid degradation of REDD2 was mediated by the UPS, the E3 ligase HUWE1, and K119/K120 of REDD2. The findings support that the cellular abundance of both REDD1 and REDD2 are controlled at the level of protein stability. - Source: PubMed
Publication date: 2025/06/28
VanCleave Ashley MSunilkumar SiddharthMcCurry Christopher MToro Allyson LKimball Scot RDennis Michael D - Pancreatic β-cells play a critical role in glucose homeostasis by secreting insulin. Chronic oxidative stress causes β-cell dysfunction, including β-cell loss; however, the underlying mechanisms remain unclear. Here, we demonstrate the critical role of the regulated in development and DNA damage response 2 (REDD2/DDiT4L/Rtp801L) in β-cell dysfunction. In INS-1 β-cells, Redd2 was induced by high glucose/palmitate or streptozotocin (STZ) exposure. Knockdown of Redd2 attenuated STZ-induced loss of cell viability, while REDD2 overexpression reduced cell viability and p70S6K phosphorylation, suggesting the involvement of suppression of mTORC1 activation. STZ also activated the transcription factors nuclear factor erythroid 2-related factor 2 (Nrf2) and p53, and overexpression of these transcription factors synergistically induced Redd2 expression. Reporter assays using the Redd2 promoter (-2328/-1) and chromatin immunoprecipitation identified the functional binding sites for Nrf2 (EpRE2, -349/-340) and p53 (p53RE1, -90/-81) on the Redd2 promoter. Purified recombinant p53 and Nrf2 bound directly. There were no noticeable changes in male global Redd2-knockout mice (C57BL/6J background), except for inguinal adipose tissue decrease when the mice were fed a standard diet. In contrast, when the mice were fed a high-fat diet (HFD), Redd2-knockout mice exhibited improved glucose tolerance relative to littermate controls. Redd2-knockout in HFD-fed mice increased β-cell mass due to reduced β-cell apoptosis and elevated plasma insulin concentrations, whereas insulin sensitivity remained unaffected. In both STZ-induced male and female and HFD-fed male models, β-cell-specific Redd2-knockout improved glucose tolerance without affecting insulin sensitivity. Our results identify REDD2 as a novel regulator of β-cell dysfunction under oxidative stress. - Source: PubMed
Publication date: 2025/05/21
Yamada YukihoUrakawa NatsuhoTamiya HisatoSakamoto ShuyaTakahashi HirokiHarada NaokiKitakaze TomoyaIzawa TakeshiMatsumua ShigenobuYoshihara EijiInui HiroshiMashimo TomojiYamaji Ryoichi - - Source: PubMed
Publication date: 2025/02/11
Li Kai-ChengShi Hai-XiangLi ZhenYou PuPan JingCai Yi-ChuanLi Jin-WenMa Xue-FeiZhang ShuoDiao LeiCai BingWang Hai-BoChen LiangMao YingZhang Xu - Brucellosis remains a significant public health issue in some parts of the world. It is clear that new laboratory methods are needed to diagnose brucellosis. Currently, no test method meets the criteria of high specificity, sensitivity, reliability, and low cost for the diagnosis of brucellosis, which could also predict chronicity. This study was conducted based on the data from a study conducted in 2015, which aimed to reveal genes with different transcript levels in chronic and acute patients and to evaluate their effects on the progression to chronicity by studying mRNA microarray and miRNA array in peripheral blood mononuclear cells in acute, chronic brucellosis and healthy control groups. According to the data obtained in this study, a second study was conducted to determine new markers that could aid in diagnosis and/or predict chronicity, with the most prominent gene products being [ABI3 (ABL interactor), PIAS4 (Protein Inhibitor of Activated STAT 4), PPP2R4 (Protein Phosphatase 2 Phosphatase Activator), DDIT4L (DNA Damage Inducible Transcript 4 Like), WDR33 (WD Repeat-Containing Protein 33), and IDO (Indoleamine 2,3-Dioxygenase)]. The study speculates that increased levels of ABI3, CLEC12B, PPP2R4 and decreased levels of DDIT4L, PIAS4, and IDO may be used as markers for the diagnosis of acute brucellosis, decreased levels of ABI3, CLEC12B, PPP2R4 and increased levels of DDIT4L, PIAS4, IDO may be assessed for treatment response. The study also suggested that maintaining consistent levels of ABI3, CLEC12B, PIAS4, PPP2R4, and IDO in subsequent titers may serve as a potential marker to predict chronic progression. - Source: PubMed
Publication date: 2024/11/07
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