PMID- 9632111
OWN - NLM
STAT- MEDLINE
DCOM- 19980812
LR  - 20061115
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 70
IP  - 1
DP  - 1998 Jul 1
TI  - Novel nuclear localization signal between the two DNA-binding zinc fingers in the 
      human vitamin D receptor.
PG  - 94-109
AB  - The human vitamin D receptor (hVDR) possesses a unique array of five basic amino 
      acids positioned between the two DNA-binding zinc fingers that is similar to 
      well-characterized nuclear localization sequences in other proteins. When 
      residues within this region are mutated to nonbasic amino acids, or when this 
      domain is deleted, the receptor is still well expressed, but it no longer 
      associates with the vitamin D-responsive element in DNA, in vitro, and 
      hVDR-mediated transcriptional activation is abolished in transfected cells. 
      Concomitantly, the mutated hVDRs exhibit a significant shift in hVDR cellular 
      distribution favoring cytoplasmic over nuclear retention as assessed by 
      subcellular fractionation and immunoblotting. Independent immunocytochemical 
      studies employing a VDR-specific monoclonal antibody demonstrate that mutation or 
      deletion of this basic domain dramatically attenuates hVDR nuclear localization 
      in transfected COS-7 cells. Although wild-type hVDR is partitioned predominantly 
      to the nucleus in the absence of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 
      hormone, treatment with ligand further enhances nuclear translocation, as it does 
      to some degree in receptors with the basic region altered. The role of 
      1,25(OH)2D3 may be to facilitate hVDR heterodimerization with retinoid X 
      receptors, stimulating subsequent DNA binding and ultimately enhancing nuclear 
      retention. Taken together, these data reveal that the region of hVDR between 
      Arg-49 and Lys-55 contains a novel constitutive nuclear localization signal, 
      RRSMKRK.
FAU - Hsieh, J C
AU  - Hsieh JC
AD  - Department of Biochemistry, The University of Arizona Health Sciences Center, 
      Tucson 85724, USA. jchsieh@medbioc.arizona.edu
FAU - Shimizu, Y
AU  - Shimizu Y
FAU - Minoshima, S
AU  - Minoshima S
FAU - Shimizu, N
AU  - Shimizu N
FAU - Haussler, C A
AU  - Haussler CA
FAU - Jurutka, P W
AU  - Jurutka PW
FAU - Haussler, M R
AU  - Haussler MR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (Receptors, Calcitriol)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blotting, Western
MH  - COS Cells
MH  - Conserved Sequence
MH  - DNA-Binding Proteins/*chemistry
MH  - Humans
MH  - Immunohistochemistry
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - *Nuclear Localization Signals
MH  - Protein Binding
MH  - Receptors, Calcitriol/*chemistry/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Subcellular Fractions/chemistry
MH  - Transcription, Genetic
MH  - *Zinc Fingers
EDAT- 1998/06/19 02:03
MHDA- 2000/06/20 09:00
CRDT- 1998/06/19 02:03
PHST- 1998/06/19 02:03 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/06/19 02:03 [entrez]
AID - 10.1002/(SICI)1097-4644(19980701)70:1<94::AID-JCB10>3.0.CO;2-B [pii]
PST - ppublish
SO  - J Cell Biochem. 1998 Jul 1;70(1):94-109.