Wilms Tumor Suppressor 1 (WT1) and Early Growth Response 1 (EGR1) Are Regulators of STIM1 Expression

Ritchie, Michael; Yue, Chanyu; Zhou, Yandong; Houghton, Peter J.; Soboloff, Jonathan

doi:10.1074/jbc.m109.083493

Cited by 51 publications

(69 citation statements)

References 41 publications

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“…The first of these does not contact the bases (Stoll et al 2007) and contributes little to specificity (Hamilton et al 1995;Nakagama et al 1995). Consequently, WT1 binds the same consensus sequence as Egr1/Zif268 (Stoll et al 2007) and, in some cases, antagonizes Egr1/Zif268 function (Ritchie et al 2010). For the work described here, we used a construct of WT1 containing only ZnF2 through ZnF4, which was structurally analogous to Egr1/Zif268.…”

Section: Resultsmentioning

confidence: 99%

Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence

et al. 2014

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In mammalian DNA, cytosine occurs in several chemical forms, including unmodified cytosine (C), 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5mC is a major epigenetic signal that acts to regulate gene expression. 5hmC, 5fC, and 5caC are oxidized derivatives that might also act as distinct epigenetic signals. We investigated the response of the zinc finger DNAbinding domains of transcription factors early growth response protein 1 (Egr1) and Wilms tumor protein 1 (WT1) to different forms of modified cytosine within their recognition sequence, 59-GCG(T/G)GGGCG-39. Both displayed high affinity for the sequence when C or 5mC was present and much reduced affinity when 5hmC or 5fC was present, indicating that they differentiate primarily oxidized C from unoxidized C, rather than methylated C from unmethylated C. 5caC affected the two proteins differently, abolishing binding by Egr1 but not by WT1. We ascribe this difference to electrostatic interactions in the binding sites. In Egr1, a negatively charged glutamate conflicts with the negatively charged carboxylate of 5caC, whereas the corresponding glutamine of WT1 interacts with this group favorably. Our analyses shows that zinc finger proteins (and their splice variants) can respond in modulated ways to alternative modifications within their binding sequence.

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Section: Resultsmentioning

confidence: 99%

Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence

et al. 2014

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“…Only recently, STIM1 and Orai1 were shown to play an important role in breast cancer cell migration and metastasis using the MDA-MB231 ER Ϫ cell model (46). Ritchie et al demonstrated that STIM1 gene expression in primary Wilms tumors is reciprocally regulated by Wilms tumor suppressor 1 (WT1) and early growth response 1 (EGR1) (47). The expression and role of STIM/Orai isoforms in ER ϩ breast cancer progression is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

A Novel Native Store-operated Calcium Channel Encoded by Orai3

Motiani

Abdullaev

Trebak

2010

Journal of Biological Chemistry

285

177

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Breast cancer is the most widespread cancer in women accounting for almost a third of all new cancer cases among women in Western countries(1, 2). Whereas most breast cancers express hormone receptors, primarily estrogen receptors (ER), 2 and depend on these hormones for their growth, an estimated 15-20% of all cases harbor the triple-negative (estrogen receptor/progesterone receptor/epidermal growth factor receptor 2-negative) phenotype (3, 4). Although breast cancer tumors are widely heterogeneous, the presence or absence of estrogen receptors on breast tumor cells represents one of the main criteria used for prognosis and for choice of hormonal and chemotherapeutic drugs.Store-operated calcium (Ca 2ϩ ) entry (SOCE) is a ubiquitous pathway necessary for refilling internal Ca 2ϩ stores and for signaling downstream to the nucleus(5-9). SOCE have been implicated in many cell functions such as proliferation, migration, and differentiation (5, 10 -12). However, a thorough characterization of the SOCE pathway in estrogen receptor-positive (ER ϩ ) and negative (ER Ϫ ) breast cancer cells is so far missing. Upon store depletion, the Ca 2ϩ sensor STIM1, that resides in the endoplasmic reticulum, oligomerizes and translocates to subplasmalemmal puncta (13,14) where it activate Orai1 channels located in the plasma membrane that mediate highly Ca 2ϩ -selective currents(15-17). Mammals possess three Orai proteins (Orai1/2/3) (15); Orai1 and Orai3 are highly expressed in similar tissues including liver, lymphoid organs, skin, and skeletal muscle (18,19). However, Orai2 is mainly found in lung, brain, spleen, and kidney (20, 21). Orai1 proteins were shown to encode the archetypical SOCE current called Ca 2ϩ release-activated Ca 2ϩ current (I CRAC )(15, 22); I CRAC was first recorded by Hoth and Penner in RBL mast cells(23). Since their discovery three years ago, Orai1, along with STIM1, were shown to be the predominant contributors to SOCE in many cell types, including T cells, B cells, mast cells, platelets, endothelial cells, smooth muscle cells, microglia, human embryonic kidney cells (HEK293), hepatocytes, and oocytes (10, 11, 15, 18, 19, 22, 24 -28). However, the role of Orai2 and Orai3 in mediating native SOCE pathways and CRAC currents remain unknown. Here we show the first evidence for I CRAC in breast cancer cells and for a native SOCE/I CRAC pathway mediated by Orai3. We demonstrate that the SOCE pathway is mediated by STIM1/2 and Orai3 proteins in ER ϩ breast cancer cells whereas the canonical STIM1/Orai1 encodes the SOCE pathway in ER Ϫ breast cancer cells. MATERIALS AND METHODSReagents-Thapsigargin, 2-APB, and nimodipine were purchased from Calbiochem, Fura-2AM was from Molecular Probes and GdCl 3 was from Acros Organics. Cs ϩ BAPTA and Pluronic F-127 were from Invitrogen. siRNAs were purchased from Dharmacon (see supplemental Table S2 for sequences). All the cell lines were bought from ATCC. All primers were synthesized by Integrated DNA Technologies. The transfection kit (VCA-1003) was from Lonza. All other ch...

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“…The molecular mechanisms directing Ca 2ϩ -dependent PMCA induction in these different systems are presently unknown. Induction of the ER calcium sensors STIM1 and STIM2 is mediated by Erg1-binding sites present in their promoters and follows calcium entry and CREB phosphorylation (61). Because STIM proteins and the Ca 2ϩ -selective Orai1 channel form the molecular substrate for store-operated calcium entry, their induction upon T cell activation represents another example of Ca 2ϩ -dependent transcriptional regulation of calcium homeostasis.…”

Section: Regulation Of Sodium/calcium Exchangers and Calcium Pumpsmentioning

confidence: 99%

Ca2+-dependent Transcriptional Control of Ca2+ Homeostasis

Naranjo

Mellström

2012

Journal of Biological Chemistry

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Intracellular free Ca2؉ ions regulate many cellular functions, and in turn, the cell devotes many genes/proteins to keep tight control of the level of intracellular free Ca 2؉ . Here, we review recent work on Ca 2؉ -dependent mechanisms and effectors that regulate the transcription of genes encoding proteins involved in the maintenance of the homeostasis of Ca 2؉ in the cell.Control of intracellular free calcium is a delicate balance between mechanisms that provide the ion, including extracellular membrane calcium channels (voltage-, ligand-, and storeoperated types) and intracellular calcium release channels (ryanodine (RyR) 2 and inositol 1,4,5-trisphosphate (IP 3 R) receptors), and mechanisms that clear the ion from the cytosol, including calcium pumps and exchangers that are localized both in extra-and intracellular membranes (1, 2). Consolidated evidence, as well as recent evidence, indicates that this group of proteins, with the mission to keep tight control of free Ca 2ϩ concentration, is in turn subjected to regulation by several mechanisms controlled by changes in free Ca 2ϩ concentration. In some cases, these self-regulatory processes involve parallel compensatory changes in several Ca 2ϩ regulatory proteins so that increases or decreases in intracellular stores and cytosolic Ca 2ϩ levels slowly adjust the concentrations of key signaling pathway components (3). In other cases, components of the homeostasis machinery are coordinately modified to respond to chronic pathological conditions as in end stages of heart failure (4, 5) or in neurodegenerative processes. Thus, in Huntington disease striatal neurons accumulate changes in the expression of most, if not all, genes related to Ca 2ϩ homeostasis (6). Also, in Alzheimer disease (AD), changes in the expression of RyRs and STIM (stromal interacting molecule) have been observed in the hippocampus of presymptomatic AD mouse models (7) and post-mortem human brain samples (8) and in B lymphocytes from patients with familial AD mutations in the presenilin-1 gene (9), respectively. Of the different control mechanisms, here we will review those that control Ca 2ϩ homeostasis at the transcriptional level and that are directly regulated by Ca 2ϩ . A review of the transcriptional control of calcium homeostasis, with particular emphasis on the roles of members of the Egr (early growth response) family of zinc finger immediate-early transcription factors and the closely related protein WT1 (Wilms tumor suppressor 1), has been published recently (10).Control of the activity of specific transcriptional networks by Ca 2ϩ is regulated by cytosolic and nuclear mechanisms that decode the calcium signal specificity in terms of frequency and spatial properties. Thus, the Ca 2ϩ entry site (synaptic versus extrasynaptic) or its intracellular source (mitochondria, endoplasmic reticulum (ER), or Golgi apparatus) makes the Ca 2ϩ ions face different microdomains that are composed of specific sets of proteins and determines the biological outcome of the Ca 2ϩ signal by inducing t...

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Wilms Tumor Suppressor 1 (WT1) and Early Growth Response 1 (EGR1) Are Regulators of STIM1 Expression

Cited by 51 publications

References 41 publications

Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence

Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence

A Novel Native Store-operated Calcium Channel Encoded by Orai3

Ca2+-dependent Transcriptional Control of Ca2+ Homeostasis

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