Identification and Characterization of the Egr-1 Gene Product, a DNA-Binding Zinc Finger Protein Induced by Differentiation and Growth Signals

Cao, Xinmin; Koski, Raymond A.; Gashler, Andrea; McKiernan, M. A.; Morris, Charles F.; Gaffney, Robert A.; Hay, Robert J.; Sukhatme, V P

doi:10.1128/mcb.10.5.1931-1939.1990

Cited by 17 publications

(2 citation statements)

References 35 publications

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“…Mutational analysis together with DNA–protein binding also suggest the importance of Egr‐1 factor for promoter activity. Egr‐1, a member of immediate early Jun/Fos family genes, was suggested to be activated by phosphorylation (Cao et al ., 1990; Huang and Adamson, 1994). Rat cathepsin L gene is reported to be activated by Egr family proteins (Ishidoh et al ., 1997).…”

Section: Discussionmentioning

confidence: 99%

Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion

et al. 2001

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Recently we showed that partial depletion of mitochondrial DNA (genetic stress) or treatment with mitochondrial-speci®c inhibitors (metabolic stress) induced a stress signaling that was associated with increased cytoplasmic-free Ca 2+ [Ca 2+ ] c . In the present study we show that the mitochondria-tonucleus stress signaling induces invasive phenotypes in otherwise non-invasive C2C12 myoblasts and human pulmonary carcinoma A549 cells. Tumor-speci®c markers cathepsin L and transforming growth factor b (TGFb) are overexpressed in cells subjected to mitochondrial genetic as well as metabolic stress. C2C12 myoblasts subjected to stress showed 4-to 6-fold higher invasion through reconstituted Matrigel membrane as well as rat tracheal xenotransplants in Scid mice. Activation of Ca 2+ -dependent protein kinase C (PKC) under both genetic and metabolic stress conditions was associated with increased cathepsin L gene expression, which contributes to increased invasive property of cells. Reverted cells with~70% of control cell mtDNA exhibited marker mRNA contents, cell morphology and invasive property closer to control cells. These results provide insights into a new pathway by which mitochondrial DNA and membrane damage can contribute to tumor progression and metastasis.

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Section: Discussionmentioning

confidence: 99%

Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion

et al. 2001

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“…EGR1 is a member of the zinc finger transcription factor family [26,27] that plays a key role in cell growth, proliferation, differentiation, and apoptosis [28]. EGR1 can behave as either an oncogene or a tumor suppressor depending on the cellular context [11][12][13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Direct early growth response-1 knockdown decreases melanoma viability independent of mitogen-activated extracellular signal-related kinase inhibition

Miley,

Andrews-Pfannkoch,

Pulido

et al. 2023

Melanoma Research

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To investigate downstream molecular changes caused by mitogen-activated protein kinase (MEK) inhibitor treatment and further explore the impact of direct knockdown of early growth response-1 (EGR1) in melanoma cell culture. RNA-sequencing (RNA-Seq) was performed to determine gene expression changes with MEK inhibitor treatment. Treatment with MEK inhibitor (trametinib) was then assessed in two cutaneous (MEL888, MEL624) and one conjunctival (YUARGE 13-3064) melanoma cell line. Direct knockdown of EGR1 was accomplished using lentiviral vectors containing shRNA. Cell viability was measured using PrestoBlueHS Cell Viability Reagent. Total RNA and protein were assessed by qPCR and SimpleWestern. RNA-Seq demonstrated a profound reduction in EGR1 with MEK inhibitor treatment, prompting further study of melanoma cell lines. Following trametinib treatment of melanoma cells, viability was reduced in both cutaneous (MEL888 26%, P < 0.01; MEL624 27%, P < 0.001) and conjunctival (YUARGE 13-3064 33%, P < 0.01) melanoma compared with DMSO control, with confirmed EGR1 knockdown to 0.04-, 0.01-, and 0.16-fold DMSO-treated levels (all P < 0.05) in MEL888, MEL624, and YUARGE 13-3064, respectively. Targeted EGR1 knockdown using shRNA reduced viability in both cutaneous (MEL624 78%, P = 0.05) and conjunctival melanoma (YUARGE-13-3064 67%, P = 0.02). RNA-Sequencing in MEK inhibitor-treated cells identified EGR1 as a candidate effector molecule of interest. In a malignant melanoma cell population, MEK inhibition reduced viability in both cutaneous and conjunctival melanoma with a profound downstream reduction in EGR1 expression. Targeted knockdown of EGR1 reduced both cutaneous and conjunctival melanoma cell viability independent of MEK inhibition, suggesting a key role for EGR1 in melanoma pathobiology.

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GTPase deficient mutant of Gα13 regulates the expression of Egr-1 through the small GTPase Rho

Prasad

Dhanasekaran

1999

Oncogene

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The a-subunit of the heterotrimeric G protein G13 regulate cell growth, di erentiation and apoptosis in di erent cell types. Expression of the constitutively activated mutant of Ga 13 (Ga 13 QL) increases the expression of Egr-1, an immediate-early response gene that is identi®ed to be involved in cell growth, di erentiation, and apoptosis. Here we report that Ga 13 QL activates the promoter of Egr-1 through speci®c sequence which includes the characteristic CArG boxes. We also demonstrate that the Ga 13 QL activation of Egr-1 promoter is mediated by the Ras-like small GTPase Rho.

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Identification and Characterization of the Egr-1 Gene Product, a DNA-Binding Zinc Finger Protein Induced by Differentiation and Growth Signals

Cited by 17 publications

References 35 publications

Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion

Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion

Direct early growth response-1 knockdown decreases melanoma viability independent of mitogen-activated extracellular signal-related kinase inhibition

GTPase deficient mutant of Gα13 regulates the expression of Egr-1 through the small GTPase Rho

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