Response element binding proteins and intracellular vitamin D binding proteins: novel regulators of vitamin D trafficking, action and metabolism.
Using vitamin D-resistant New World primates as model of natural diversity for sterol/steroid action and metabolism, two families of novel intracellular vitamin D regulatory proteins have been discovered and their human homologs elucidated. The first family of proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs), initially considered to function only as pre-mRNA-interacting proteins, have been demonstrated to be potent cis-acting, trans-dominant regulators of vitamin D hormone-driven gene transactivation. The second group of proteins bind 25-hydroxylated vitamin D metabolites. Their overexpression increases vitamin D receptor (VDR)-directed target gene expression. We found that these intracellular vitamin D binding proteins (IDBPs) are homologous to proteins in the heat shock protein-70 family. Our ongoing studies indicate directly or indirectly through a series of protein interactions that the IDBPs interact with hydroxylated vitamin D metabolites and facilitate their intracellular targeting.
Adams
John S
JS
The Burns and Allen Research Institute, Cedars-Sinai Medical Center, UCLA School of Medicine, B131, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, USA.
Chen
Hong
H
Chun
Rene
R
Gacad
Mercedes A
MA
Encinas
Carlos
C
Ren
Songyang
S
Nguyen
Lisa
L
Wu
Shaoxing
S
Hewison
Martin
M
Barsony
Julia
J
D000818:Animals; D004196:Disease Outbreaks; D006801:Humans; D012279:Rickets / Q000453:epidemiology; D014807:Vitamin D / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000378:metabolism*
D014809:Vitamin D-Binding Protein; D014807:Vitamin D