Abstract
UV irradiation of normal or immortalized cells induces a rapid increase in the expression of several transcription factors and is thought to serve a protective function. The human fibrosarcoma cell line, HT1080 clone H4, expresses almost undetectable levels of Egr-1 and does not respond to UV-C irradiation by the induction of Egr-1. The H4 cells are hypersensitive to UV which induces apoptosis and reduces clonogenicity. The introduction of exogenous Egr-1 into H4 (H4E9 and H4E4 cell-lines) confers protection from UV damage as measured by a number of assays. In both NIH3T3 (with inducible Egr-1) and H4E9 (constitutive Egr-1) cells, UV irradiation gave enhanced transactivation of Egr-1 reporters that correlated with phosphorylated Egr-1. Studies using inhibitors indicated that protein kinase-C and tyrosine kinases are involved in the anti-apoptotic effects of Egr-1 after UV damage. This is the first description of a biological effect of phosphorylated Egr-1.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells / chemistry
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3T3 Cells / cytology
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Animals
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Apoptosis / physiology*
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Apoptosis / radiation effects*
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Cell Survival / physiology
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Cell Survival / radiation effects
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Choline O-Acetyltransferase / genetics
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Early Growth Response Protein 1
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Fibrosarcoma
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G2 Phase / physiology
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Gene Expression Regulation, Enzymologic
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Humans
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Immediate-Early Proteins*
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Mice
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Phosphorylation
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Protein Kinase C / metabolism
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Protein-Tyrosine Kinases / metabolism
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S Phase / physiology
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcriptional Activation / physiology
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Tumor Cells, Cultured / chemistry
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / enzymology
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Ultraviolet Rays
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Zinc Fingers / physiology*
Substances
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DNA-Binding Proteins
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EGR1 protein, human
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Early Growth Response Protein 1
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Egr1 protein, mouse
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Immediate-Early Proteins
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Transcription Factors
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Choline O-Acetyltransferase
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Protein-Tyrosine Kinases
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Protein Kinase C