PMID- 19931640
OWN - NLM
STAT- MEDLINE
DCOM- 20100429
LR  - 20211020
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Print)
IS  - 1357-2725 (Linking)
VI  - 42
IP  - 2
DP  - 2010 Feb
TI  - Vitamin D receptor deletion leads to reduced level of IkappaBalpha protein 
      through protein translation, protein-protein interaction, and post-translational 
      modification.
PG  - 329-36
LID - 10.1016/j.biocel.2009.11.012 [doi]
AB  - Vitamin D receptor plays an essential role in the regulation of inflammation. 
      Previous studies demonstrate that vitamin D receptor negatively modulates the 
      proinflammatory NF-kappaB pathway. However, it is unknown how vitamin D receptor 
      regulates IkappaBalpha, the endogenous inhibitor of NF-kappaB. Here we 
      investigated the molecular mechanism of vitamin D receptor deletion and 
      IkappaBalpha expression. We found that cells lacking vitamin D receptor had 
      significantly increased levels of IkappaBalpha mRNA and simultaneously decreased 
      levels of IkappaBalpha protein. Lacking vitamin D receptor abolished its binding 
      to the IkappaBalpha promoter. Moreover, the levels of protein translation 
      regulators and the rate of protein synthesis were both decreased in cells lacking 
      vitamin D receptor. At the post-translational level, IkappaBalpha ubiquitination 
      was enhanced, indicating increased degradation of IkappaBalpha in the absence of 
      vitamin D receptor. We further transfected cells with a plasmid carrying either 
      wild-type or mutant IkappaBalpha. The expression of wild-type IkappaBalpha was 
      much higher in the cells with vitamin D receptor than in the cells without 
      vitamin D receptor, whereas the expression of exogenous IkappaBalpha was equally 
      high in both cell lines. In summary, vitamin D receptor deletion affects 
      IkappaBalpha through mRNA transcription, protein translation, protein-protein 
      interaction, post-translational modification, and protein degradation, thus 
      reducing the level of IkappaBalpha protein. Cells lacking vitamin D receptor are 
      known in a proinflammatory state with activation of NF-kappaB. Our study provides 
      new insight into vitamin D receptor regulation of an inhibitor of NF-kappaB in 
      inflammation. Deletion of vitamin D receptor contributes to the activation of 
      NF-kappaB on multiple levels.
CI  - Copyright (c) 2009 Elsevier Ltd. All rights reserved.
FAU - Wu, Shaoping
AU  - Wu S
AD  - Department of Medicine, Gastroenterology & Hepatology Division, University of 
      Rochester, 601 Elmwood Ave., Rochester, NY 14642, USA.
FAU - Xia, Yinglin
AU  - Xia Y
FAU - Liu, Xingyin
AU  - Liu X
FAU - Sun, Jun
AU  - Sun J
LA  - eng
GR  - K01 DK075386/DK/NIDDK NIH HHS/United States
GR  - K01 DK075386-03/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091130
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Acetylation
MH  - Alleles
MH  - Animals
MH  - Cell Line
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Gene Deletion
MH  - Gene Expression Regulation
MH  - I-kappa B Proteins/*biosynthesis/*metabolism
MH  - Inflammation/metabolism
MH  - Mice
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/genetics
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Binding
MH  - *Protein Processing, Post-Translational
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Calcitriol/*deficiency/*genetics/metabolism
MH  - Transcription, Genetic
MH  - Ubiquitination
MH  - eIF-2 Kinase/metabolism
PMC - PMC2818560
MID - NIHMS160847
EDAT- 2009/11/26 06:00
MHDA- 2010/04/30 06:00
PMCR- 2011/02/01
CRDT- 2009/11/26 06:00
PHST- 2009/09/28 00:00 [received]
PHST- 2009/11/02 00:00 [revised]
PHST- 2009/11/12 00:00 [accepted]
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/04/30 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - S1357-2725(09)00342-2 [pii]
AID - 10.1016/j.biocel.2009.11.012 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2010 Feb;42(2):329-36. doi: 
      10.1016/j.biocel.2009.11.012. Epub 2009 Nov 30.