1: EMBO J. 1997 Jan 2;16(1):143-53. 

Cyclosporin A-sensitive induction of the Epstein-Barr virus lytic switch is
mediated via a novel pathway involving a MEF2 family member.

Liu S, Liu P, Borras A, Chatila T, Speck SH.

Department of Pathology, Children's Hospital, Washington University School of
Medicine, St. Louis, MO 63110, USA.

Induction of the Epstein-Barr virus (EBV) lytic cycle by crosslinking surface
immunoglobulin is inhibited by the immunosuppressants cyclosporin A (CsA) and
FK506. This correlates with the ability of CsA to inhibit Ca2+-dependent
transcription of the lytic cycle switch gene BZLF1. It is shown here that CsA
sensitivity maps to three sites (ZIA, ZIB and ZID) that bind the serum response
factor-related protein MEF2D. A synthetic promoter containing multiple copies of
a MEF2D site from Zp, in conjunction with a CREB/AP-1 site (ZII) from Zp,
exhibits CsA-sensitive inducibility. Furthermore, the Zp MEF2D sites were
functionally interchangeable with MEF2 sites derived from heterologous
promoters. While no evidence of a NFAT family member binding to either the MEF2
or CREB/AP-1 sites was obtained, it could be demonstrated that CsA-sensitive
induction of Zp was mediated by calcineurin and NFATc2 in synergy with either
phorbol ester or especially with the EBV-induced Ca2+/calmodulin-dependent
kinase type IV/Gr. These studies identify Zp as prototypic of a novel class of
CsA-sensitive and NFAT-dependent promoters defined by the presence of MEF2
sites.

PMID: 9009275 [PubMed - indexed for MEDLINE]


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