Niemann-Pick C1 Disease Gene: Homology to Mediators of Cholesterol Homeostasis
Open Access
- 11 July 1997
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 277 (5323) , 228-231
- https://doi.org/10.1126/science.277.5323.228
Abstract
Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)–derived cholesterol. By positional cloning methods, a gene ( NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278–amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.Keywords
This publication has 20 references indexed in Scilit:
- Human Homolog of patched , a Candidate Gene for the Basal Cell Nevus SyndromeScience, 1996
- Sterol-Regulated Release of SREBP-2 from Cell Membranes Requires Two Sequential Cleavages, One Within a Transmembrane SegmentCell, 1996
- Regulated Cleavage of Sterol Regulatory Element Binding Proteins Requires Sequences on Both Sides of the Endoplasmic Reticulum MembranePublished by Elsevier ,1996
- SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysisCell, 1994
- A novel di-leucine motif and a tyrosine-based motif independently mediate lysosomal targeting and endocytosis of CD3 chainsCell, 1992
- Type-C Niemann-Pick disease: low density lipoprotein uptake is associated with premature cholesterol accumulation in the Golgi complex and excessive cholesterol storage in lysosomes.Proceedings of the National Academy of Sciences, 1988
- A Receptor-Mediated Pathway for Cholesterol HomeostasisScience, 1986
- On the predictive recognition of signal peptide sequencesVirus Research, 1985
- Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulumNature, 1984
- A comprehensive set of sequence analysis programs for the VAXNucleic Acids Research, 1984