Transcription factor Egr-1 activity down-regulates Fas and CD23 expression in B cells.
Activation of mature B cells via Ag receptor cross-linking induces transient expression of the transcription factor Egr-1. Although the activating signals leading to Egr-1 induction have been studied extensively, little is known about the genes that are placed further downstream within this activation cascade and that are transcriptionally regulated by Egr-1. To identify such target genes, we established Egr-1-overexpressing transfectants from the murine B cell line K46 and from human Ramos B cells. All clones derived from K46 B cells showed increased expression of CD44. Most interestingly, expression of CD95 (Fas/Apo-1) and of CD23 was down-regulated in all K46 transfectants. As a consequence, they became resistant to apoptosis induced by anti-CD95 Ab treatment. Similarly, the Egr-1-expressing Ramos cells showed reduced levels of CD95 expression. Thus, Egr-1 seems to control the expression of downstream target genes not only as a transcriptional activator, but also as a repressor molecule. In B cells, Egr-1 therefore plays a critical role in integrating the short-lived signal delivered by triggering of the Ag receptor into phenotypic changes, including repression of CD95 and CD23 transcription.
Dinkel
A
A
University Hospital Freiburg, Department of Biology, University of Freiburg, Germany.
Aicher
W K
WK
Haas
C
C
Zipfel
P F
PF
Peter
H H
HH
Eibel
H
H
D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D051766:Early Growth Response Protein 1; D018014:Gene Transfer Techniques; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers; D019014:fas Receptor / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D017455:Receptors, IgE; D014157:Transcription Factors; D019014:fas Receptor