PUBLICATION
The non-canonical NF-κB pathway promotes NPC2 expression and regulates intracellular cholesterol trafficking
- Authors
- Liao, Y., Wei, J., Wang, J., Shi, X., Luo, J., Song, B.L.
- ID
- ZDB-PUB-180810-8
- Date
- 2018
- Source
- Science China. Life sciences 61(10): 1222-1232 (Journal)
- Registered Authors
- Keywords
- NF-κB2, NPC2, cholesterol transport, transcriptional regulation
- MeSH Terms
-
- Animals
- Biological Transport
- Carrier Proteins/genetics
- Carrier Proteins/metabolism*
- Cell Line
- Cell Line, Tumor
- Cells, Cultured
- Cholesterol/metabolism*
- Embryo, Nonmammalian/metabolism
- Glycoproteins/genetics
- Glycoproteins/metabolism*
- HeLa Cells
- Humans
- Intracellular Space/metabolism
- Mice, Knockout
- Microscopy, Confocal
- NF-kappa B p52 Subunit/genetics
- NF-kappa B p52 Subunit/metabolism*
- RNA Interference
- Signal Transduction*
- Zebrafish
- PubMed
- 30091016 Full text @ Sci. China Ser. C-Life Sci.
Citation
Liao, Y., Wei, J., Wang, J., Shi, X., Luo, J., Song, B.L. (2018) The non-canonical NF-κB pathway promotes NPC2 expression and regulates intracellular cholesterol trafficking. Science China. Life sciences. 61(10):1222-1232.
Abstract
Niemann-Pick type C2 (NPC2) is a lysosome luminal protein that functions in concert with NPC1 to mediate egress of low-density lipoprotein-derived cholesterol from lysosome. The nuclear factor kappa B subunit 2 (NF-κB2) protein is a component of NF-κB transcription factor complex critically implicated in immune and inflammatory responses. Here, we report that NF-κB2 regulates intracellular cholesterol transport by controlling NPC2 expression. RNAi-mediated disruption of NF-κB2, as well as other signaling members of the non-canonical NF-κB pathway, caused intracellular cholesterol accumulation. Blockage of the non-canonical NF-κB pathway suppressed NPC2 expression, whereas Lymphotoxin β receptor (LTβR) activation or Baff receptor (BaffR) stimulation up-regulated the mRNA abundance and protein level of NPC2. Further, NF-κB2 activated NPC2 transcription through direct binding to its promoter region. We also observed cholesterol accumulation in NF-κB2-deficient zebrafish embryo and NF-κB2 mutant mice. Collectively, these data identify a regulatory role for the non-canonical NF-κB pathway in intracellular cholesterol trafficking and suggest a link between cholesterol transport and immune system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping