Egr-1 inhibits apoptosis during the UV response: correlation of cell survival with Egr-1 phosphorylation.
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.
Huang
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RP
Molecular Medicine, Northwest Hospital, 120 Northgate Plaza, Suite 230, Seattle, Washington 98125, USA.
Fan
Y
Y
deBelle
I
I
Ni
Z
Z
Matheny
W
W
Adamson
E D
ED
D016475:3T3 Cells / Q000737:chemistry / Q000166:cytology; D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D002795:Choline O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005354:Fibrosarcoma; D016195:G2 Phase / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017874:Immediate-Early Proteins; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D014466:Ultraviolet Rays; D016335:Zinc Fingers / Q000502:physiology*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D002795:Choline O-Acetyltransferase; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C