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J Biol Chem, Vol. 274, Issue 27, 19352-19360, July 2, 1999
Hormone-dependent Translocation of Vitamin D
Receptors Is Linked to Transactivation
Attila
Racz and
Julia
Barsony
From the Laboratory of Cell Biochemistry and Biology, NIDDK,
National Institutes of Health, Bethesda, Maryland 20892
Vitamin D receptor (VDR) acts as a transcription
factor mediating genomic actions of calcitriol. Our earlier studies
suggested that calcitriol induces translocation of cytoplasmic VDR, but the physiologic relevance of this finding remained uncertain. Previous
studies demonstrated that the activation function 2 domain (AF-2) plays
an essential role in VDR transactivation. To elucidate hormone-dependent VDR translocation and its role, we
constructed green fluorescent protein (GFP) chimeras with full-length
VDR (VDR-GFP), AF-2-truncated VDR (AF-2del-VDR-GFP), and ligand-binding domain (LBD)-truncated VDR (LBDdel-VDR-GFP). COS-7 cells were transiently transfected with these constructs. Western blot analysis, fluorescent microscopy, and transactivation assays showed that the
generated chimeras are expressed and fluoresce and that VDR-GFP is
transcriptionally active. After hormone treatment, cytoplasmic VDR-GFP
translocated to the nucleus in a concentration-, time-, temperature-,
and analog-specific manner. Hormone dose-response relationships for
translocation and for transactivation were similar. Truncation of LBD
and truncation of AF-2 each abolished hormone-dependent translocation and transactivation. Our data confirm a
hormone-dependent VDR translocation, demonstrate that an
intact AF-2 domain is required for this translocation, and indicate
that translocation is part of the receptor activation process.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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