A New Member of the Leucine Zipper Class of Proteins that Binds to the HLA DRα Promoter

Liou, Hsiou‐Chi; Boothby, Mark; Finn, Patricia W.; Davidon, Ruth; Nabavi, Nasrin; Zeleznik‐Le, Nancy J.; Ting, Jenny P.Y.; Glimcher, Laurie H.

doi:10.1126/science.2321018

Cited by 275 publications

(157 citation statements)

References 20 publications

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“…HNF3A was shown previously to co-cluster with ESR1 in expression profiles from 65 breast tumors by Perou et al 24 Three additional genes listed in Table 1 also co-clustered with ESR1 in the report by Perou et al: LIV-1; hepsin (HPN) a transmembrane protease which plays an essential role in cell growth and maintenance of cell morphology; 25 X-box binding protein 1 (XBP1) which binds to the HLA-DR-alpha promoter and may act as a transcription factor in B-cells. 26 Alpha-2-glycoprotein 1, zinc (AZGP1) is unique among the genes co-clustering with ESR1 in that it has not previously been associated with estrogen responsiveness but it has been considered as a biochemical marker of differentiation in breast cancer. 27 AZGP1 is a secreted protein that stimulates lipid degradation in adipocytes and may contribute to the extensive fat loss in patients with advanced cancer.…”

Section: Wwwnaturecom/tpjmentioning

confidence: 99%

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

et al. 2001

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The estrogen receptor plays a critical role in the pathogenesis and clinical behavior of breast cancer. To better understand the molecular basis of estrogen-dependent forms of this disease we studied gene expression profiles from 53 primary breast cancer biopsies. Gene expression data for more than 7000 genes were generated from each tumor sample with oligo microarrays. A standard correlation-clustering algorithm identified 18 genes that co-clustered with estrogen receptor alpha. Eleven of these genes had previously been associated with estrogen regulation or breast tumorigenesis including trefoil factor 1 and estrogen regulated LIV-1. Additional study of these 18 genes may further delineate the role of estrogen receptor in breast cancer, generate new predictive biomarkers for response to endocrine therapies and identify novel therapeutic targets. The Pharmacogenomics Journal ( BACKGROUNDThe estrogen receptor is a ligand-activated transcription factor containing hormone binding, DNA binding and transcription activation domains. 1 It is expressed in normal breast and 50-80% of breast cancers, depending on the assay used. 2-4 Estrogen receptor (ER) is a favorable prognostic factor and ER positive malignancies have a lower risk of relapse and a better overall survival. 5 However, ESR1 analysis is most useful in predicting response to endocrine therapies, although approximately half of all ER-positive cancers do not respond to antiestrogens or estrogen deprivation therapies. 6 The molecular basis for ESR1-positive, endocrine therapy-resistant disease is not well understood. Somatic mutations in ESR1 are rare, even in breast cancers that have acquired resistances to endocrine therapies. This finding has focused attention on other mechanisms, including the overexpression of tyrosone-kinase linked growth factor receptors, transcriptional coactivators such as AIB1 (amplified in breast cancer 1) or cell cycle regulators including Cyclin D1. Additional possibilities include mutations in other genes involved in the regulation of estrogen-dependent growth.Expression of the estrogen-regulated genes, progesterone receptor (PGR) and trefoil factor 1 (TFF1 or PS2) indicate the presence of a functional and activated ER. 7 Both of these proteins are predictive biomarkers for breast cancer endocrine therapy, although less valuable than ER in distinguishing estrogen-dependent from estrogen-independent breast cancer. The use of PGR improves upon the predictive value of ER alone, yet ෂ 40% of tumors that express both ER and PGR fail to respond to endocrine treatments in the metastatic setting. 8 Similarly, TFF1 is associated with a good prognosis and predicts a positive response to hormonal therapy, but it has not proved to be sufficient as a predictive biomarker for routine evaluation of breast cancer. 9 Thus, PGR and TFF1 may be modestly useful

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Section: Wwwnaturecom/tpjmentioning

confidence: 99%

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

et al. 2001

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“…Under ER-stressed conditions, the binding of misfolded proteins and/or the dissociation of chaperone GRP78 results in IRE1␣ dimerization, trans-autophosphorylation, oligomerization with the help of the actin cytoskeleton (4), and activation of its RNase activity (5,6). Activated IRE1␣ splices 26 nucleotides from the Xbp1 mRNA to generate the Xbp1s (spliced) transcript, which encodes the transcription factor XBP1s, responsible for the induction of various ER chaperones (7,8). The activation mechanism for PERK may be similar to that for IRE1␣ because their luminal domains are interchangeable (9).…”

Section: Alteration Of Endoplasmic Reticulum (Er)mentioning

confidence: 99%

Phenformin Activates the Unfolded Protein Response in an AMP-activated Protein Kinase (AMPK)-dependent Manner

Yang

Sha

Davisson

et al. 2013

Journal of Biological Chemistry

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“…sXBP1 is an active transcription factor that induces transcription of a cluster of genes to expand the folding capacity of ER, promote ER-associated retrograde transport and degradation (ERAD) of unfolded proteins, and phospholipid synthesis, thereby promoting cell survival (7)(8)(9). XBP1 was characterized in 1990 as a basic leucine zipper domain (bZIP) transcription factor in B cells (10). Activation of XBP1 in response to ER stress is well established.…”

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confidence: 99%

The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X‐box binding protein 1 transcription factor

et al. 2015

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Endoplasmic reticulum (ER) stress triggers the integrated ER-stress response (IERSR) that ensures cellular survival of ER stress and represents a primordial form of innate immunity. We investigated the role of IERSR during Leishmania amazonensis infection. Treatment of RAW 264.7 infected macrophages with the ER stress-inducing agent thapsigargin (TG; 1 mM) increased L. amazonensis infectivity in an IFN1-a receptor (IFNAR)-dependent manner. In Western blot assays, we showed that L. amazonensis activates the inositol-requiring enzyme (IRE1)/ X-box binding protein (XBP)-1-splicing arms of the IERSR in host cells. In chromatin immunoprecipitation (ChIP) assays, we showed an increased occupancy of enhancer and promoter sequences for the Ifnb gene by XBP1 in infected RAW 264.7 cells. Knocking down XBP1 expression by transducing RAW 264.7 cells with the short hairpin XBP1 lentiviral vector significantly reduced the parasite proliferation associated with impaired translocation of phosphorylated IFN regulatory transcription factor (IRF)-3 to the nucleus and a decrease in IFN1-b expression. Knocking down XBP1 expression also increased NO concentration, as determined by Griess reaction and reduced the expression of antioxidant genes, such as heme oxygenase (HO)-1, that protect parasites from oxidative stress. We conclude that L. amazonensis activation of XBP1 plays a critical role in infection by protecting the parasites from oxidative stress and increasing IFN1-b expression.-

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A New Member of the Leucine Zipper Class of Proteins that Binds to the HLA DRα Promoter

Cited by 275 publications

References 20 publications

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

Phenformin Activates the Unfolded Protein Response in an AMP-activated Protein Kinase (AMPK)-dependent Manner

The integrated endoplasmic reticulum stress response in Leishmania amazonensis macrophage infection: the role of X‐box binding protein 1 transcription factor

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