<scp>NDRG</scp>2 acts as a <scp>PERK</scp> co‐factor to facilitate <scp>PERK</scp> branch and <scp>ERS</scp>‐induced cell death

Zhang, Mei; Liu, Xiping; Wang, Qinhao; Yi, Ruokun; Xiong, Xin; Wu, Kaichun; Yao, Libo; Li, Xia

doi:10.1002/1873-3468.12861

Cited by 9 publications

(11 citation statements)

References 37 publications

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“…8. Glutamine withdrawal down-regulated the expression of most studied factors and these results completely agree with functional activity of ATF6, EIF2AK3/PERK, GLO1, BIRC5/survivin, and RAB5C proteins, which shown pro-proliferative effects [16][17][18][24][25][26][27][28][29][30][31][32].…”

Section: Fig 3 Effect Of Glutamine Deprivation On the Expression Lesupporting

confidence: 76%

“…Furthermore, ATF6 activates stress responsible gene expressions and regulates cellular senescence, which is known as an anti-tumor barrier [5,26]. Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3), which also known as PKR-like ER kinase (PERK), is an elF2alpha kinase that inhibits protein translation and is involved in control of cell proliferation and tumorigenesis, in mitochondrial function and apoptosis [27][28][29]. It is also an important signaling protein of endoplasmic reticulum stress signaling pathways [5].…”

Section: The Expression Of a Subset Of Genes Encoding Important Tumormentioning

confidence: 99%

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ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

Minchenko¹,

Kharkova²,

Hnatiuk³

2018

Ukr.Biochem.J

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Section: Fig 3 Effect Of Glutamine Deprivation On the Expression Lesupporting

confidence: 76%

Section: The Expression Of a Subset Of Genes Encoding Important Tumormentioning

confidence: 99%

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

Minchenko¹,

Kharkova²,

Hnatiuk³

2018

Ukr.Biochem.J

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“…Thus, overexpression of NDRG2 promotes ERS-induced apoptosis, while silencing or knockdown of NDRG2 does the opposite, both in cell lines and in vivo. These data suggest that NDRG2 is a novel ER stress-responsive protein and an important component of the UPRosome, acting as a PERK cofactor to facilitate PERK branch signaling and thereby contributing to ER stress-induced apoptosis [17]. Therefore, apart from its already established role, NDRG2 could be considered a component of the UPRosome and a key player in cell fate decisions during ER stress.…”

Section: The Finding Of Ndrg2mentioning

confidence: 90%

“…NDRG2 is a stress-responsive gene [1], and our laboratory recently reported that as such, NDRG2 is implicated in ER stress [17] in addition to the hypoxia and DNA damage response. Different ER stress inducers, including thapsigargin (Tg), tunicamycin (Tm) and dithiothreitol (DTT), can induce NDRG2 mRNA and protein expression in human hepatoma SK-Hep-1 and HepG2 cells.…”

Section: The Finding Of Ndrg2mentioning

confidence: 99%

N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Novel Tumor Suppressor in Multiple Human Cancers

Zhang¹,

Li²,

Shen³

et al. 2019

Genes and Cancer

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N-myc downstream-regulated gene 2 (NDRG2) was identified as a novel tumor suppressor gene in regulating the proliferation, differentiation, apoptosis and metastasis of multiple cancer types. Consistent with this finding, we and other groups observed the decreased NDRG2 expression in multiple human cancer cell lines and tumors, including breast cancer, colorectal cancer, and cervical cancer. We identified NDRG2 as a stress sensor for hypoxia, DNA damage stimuli and endoplasmic reticulum stress (ERS). Our recent data showed that NDRG2 could promote the differentiation of colorectal cancer cells. Interestingly, we found that reduced NDRG2 expression was a powerful and independent predictor of poor prognosis of colorectal cancer patients. Furthermore, NDRG2 can inhibit epithelial-mesenchymal transition (EMT) by positively regulating E-cadherin expression. Moreover, NDRG2-deficient mice show spontaneous development of various tumor types, including T-cell lymphomas, providing in vivo evidence that NDRG2 functions as a tumor suppressor gene. We believe that NDRG2 is a novel tumor suppressor and might be a therapeutic target for cancer treatment.Genes and Cancer 2 carcinoma cells [8]. Moreover, NDRG2-deficient mice show spontaneous development of various tumor types, providing in vivo evidence that NDRG2 functions as a tumor suppressor gene. In this chapter, we will introduce the recent findings of NDRG2 as tumor suppressor in vitro and in vivo, and also the detailed mechanism. NDRG2 as a hypoxia and DNA damage responderOur group firstly identified NDRG2 as a protein containing an acyl-carrier protein (ACP)-like domain. The gene was cloned from differentially expressed genes between glioblastoma and normal brain tissues using PCR-based subtractive hybridization in 2003. NDRG2, NDRG1, NDRG3, and NDRG4 comprise the NDRG gene family [1] and share approximately 59-68% homology. Additionally, NDRG family members display over 92% homology between humans and mice.The expression and cellular localization of NDRG2 were altered following exposure to different stresses, supporting the role of NDRG2 as a cellular stress sensor. Wang et al. found that NDRG2 expression was markedly upregulated in several cancer cell lines exposed to hypoxic conditions or similar stresses at both the mRNA and protein levels [9]. Hypoxia-inducible factor-1α (HIF-1α) can directly bind to hypoxia response elements (HREs) in the NDRG2 promoter, thus upregulating NDRG2 expression under hypoxia. Importantly, enforcing the expression of NDRG2 can strongly increase the apoptosis of cancer cells. Alternatively, NDRG2 can translocate from the cytoplasm to the nucleus under DNA damage stress. However, no explicit nuclear localization signal (NLS) sequence has been identified in the NDRG2 protein. Although NLSs are the most common type of nuclear import elements, other mechanisms may also be involved in NDRG2 translocation. For example, Liu et al. and Cao et al. confirmed that NDRG2 was upregulated by p53 or adriamycin (ADR) treatment [10,11]. Thus, NDRG2 can tra...

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“…Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3), which also known as PKR-like ER kinase (PERK), is an elF2alpha kinase that inhibits protein translation and is involved in control of cell proliferation and tumorigenesis, in mitochondrial function and apoptosis [44] [45] [46]. Both activating transcription factor 6 and PKR-like ER kinase (PERK) are also important signaling proteins of endoplasmic reticulum stress pathway [5].…”

mentioning

confidence: 99%

Effect of Hypoxia on the Expression of a Subset of Proliferation Related Genes in IRE1 Knockdown U87 Glioma Cells

Tsymbal¹,

Minchenko²,

Hnatiuk³

et al. 2017

ABC

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We have studied the expression of a subset of genes encoding important tumor growth related factors in U87 glioma cells with IRE1 (inositol requiring enzyme-1) knockdown as well as their hypoxic regulation. It was shown that the expression levels of activating transcription factor 6 (ATF6), clusterin (CLU), adhesion G protein-coupled receptor E5 (ADGRE5), transglutaminase 2, C polypeptide (TGM2), leukemia inhibitory factor (LIF), phosphoserine aminotransferase 1 (PSAT1), glyoxalase I (GLO1) and tetraspanin 13 (TSPAN13) are significantly down-regulated in glioma cells with the knockdown of IRE1 signaling enzyme. It was also shown that in glioma cells subjected to hypoxia, the expression levels of PSAT1, TSPAN13, EIF2AK3, and TGM2 genes were up-regulated, whereas the expression of ATF6 gene was down-regulated. At the same time, the expression levels of LIF, CLU, and ADGRE5 genes did not change in response to hypoxic treatment. Furthermore, inhibition of IRE1, a key effector of an unfolded protein response pathway, modified the effect of hypoxia on the expression of most studied genes. Present study demonstrates that IRE1 knockdown down-regulated the expression of most studied genes and modified their hypoxic regulation and that these changes possibly contributed to the suppression of glioma growth in cells without IRE1 signaling enzyme function.

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NDRG2 acts as a PERK co‐factor to facilitate PERK branch and ERS‐induced cell death

Cited by 9 publications

References 37 publications

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

ERN1 modifies the effect of glutamine deprivation on tumor growth related factors expression in U87 glioma cells

N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Novel Tumor Suppressor in Multiple Human Cancers

Effect of Hypoxia on the Expression of a Subset of Proliferation Related Genes in IRE1 Knockdown U87 Glioma Cells

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