International Immunology, Vol 9, 1885-1895, Copyright © 1997 by Oxford University Press
B Shieh, J Schultz, M Guinness and J Lacy
An early and critical event in immortalization of human B cells by
Epstein-Barr virus (EBV) is induction of CD23 expression. CD23 is
constitutively expressed in all EBV-immortalized B cells and its expression
is tightly linked with immortalization. We have previously shown that
activation of CD23 by EBV occurs at the transcriptional level and is
mediated, in part, by EBV-responsive enhancer elements in the region of the
type a promoter. We have localized one EBV-responsive enhancer (designated
EBVRE) to a 37 bp sequence in intron 1 of type a CD23 that contains a
GC-rich sequence that binds nuclear protein(s) from EBV-positive but not
EBV-negative cells with sequence specificity. This EBVRE-binding activity
was enhanced by protein phosphorylation and did not react with antibodies
to the ubiquitous GC box transcription factor, Sp1. We have now shown by
protein purification with peptide sequencing and immunological reactivity
that p70/p80 Ku autoantigen [the DNA-binding component of DNA-dependent
protein kinase (DNA-PK)] binds to this EBVRE with high affinity and
sequence specificity. Although Ku autoantigen is ubiquitously expressed, an
EBV-specific DNA- protein complex that contains Ku was elicited from
EBV-positive but not EBV-negative nuclear extracts. Furthermore, the
formation of this EBV- specific DNA-Ku complex was dramatically enhanced by
protein phosphorylation. Thus, we have identified EBVRE-binding activity
that contains the Ku autoantigen, is DNA sequence specific and is present
in EBV-positive but not EBV-negative nuclear extracts. The possible
functional significance of the Ku autoantigen-EBVRE interaction is
discussed in light of the role of DNA-PK in phosphorylation and activation
of several transcription factors. We suggest that phosphorylation of the
EBV-specific EBVRE-binding activity by DNA-PK may modulate its activity as
a transcription factor.
ARTICLES
Regulation of the human IgE receptor (Fc epsilonRII/CD23) by Epstein- Barr virus (EBV): Ku autoantigen binds specifically to an EBV- responsive enhancer of CD23
Department of Medicine, Yale University, New Haven, CT 06520, USA.
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