Nuclear UDP-glucuronosyltransferases: identification of UGT2B7 and UGT1A6 in human liver nuclear membranes.
We have demonstrated the subcellular localization of the human UDP-glucuronosyltransferases (UGTs), UGT2B7 and UGT1A6, in endoplasmic reticulum (ER) and nuclear membrane from human hepatocytes and cell lines, by in situ immunostaining and Western blot. Double immunostaining for UGT2B7 and calnexin, an ER resident protein, showed that UGT2B7 was equally present in ER and nuclear membrane whereas calnexin was present almost exclusively in ER. Immunogold labeling of HK293 cells expressing UGT2B7 established the presence of UGT2B7 in both nuclear membranes. Enzymatic assays with UGT2B7 substrates confirmed the presence of functional UGT2B7 protein in ER, whole nuclei, and both outer and inner nuclear membranes. This study has identified, for the first time, the presence of UGT2B7 and UGT1A6 in the nucleus and of UGT2B7 in the inner and outer nuclear membranes. This localization may play an important functional role within nuclei: protection from toxic compounds and/or control of steady-state concentrations of nuclear receptor ligands.
Radominska-Pandya
Anna
A
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 77205, USA. RadominskaAnna@uams.edu
Pokrovskaya
Irina D
ID
Xu
Jing
J
Little
Joanna M
JM
Jude
Anthony R
AR
Kurten
Richard C
RC
Czernik
Piotr J
PJ
D000368:Aged; D015153:Blotting, Western; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005260:Female; D005455:Fluorescent Antibody Technique; D014453:Glucuronosyltransferase / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology*; D008856:Microscopy, Fluorescence; D009685:Nuclear Envelope / Q000201:enzymology* / Q000648:ultrastructure
C110655:UDP-glucuronosyltransferase, UGT1A6; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase