Linked Life Data

10349869

Source:http://linkedlifedata.com/resource/pubmed/id/10349869

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-6-14
pubmed:abstractText
The specific accumulation of the hydrophobic protein, subunit c of ATP synthase, in lysosomes from the cells of patients with the late infantile form of neuronal ceroid lipofuscinosis (LINCL) is caused by lysosomal proteolytic dysfunction. The defective gene in LINCL (CLN2 gene) has been identified recently. To elucidate the mechanism of lysosomal storage of subunit c, antibodies against the human CLN2 gene product (Cln2p) were prepared. Immunoblot analysis indicated that Cln2p is a 46-kDa protein in normal control skin fibroblasts and carrier heterozygote cells, whereas it was absent in cells from four patients with LINCL. RT-PCR analysis indicated the presence of mRNA for CLN2 in cells from the four different patients tested, suggesting a low efficiency of translation of mRNA or the production of the unstable translation products in these patient cells. Pulse-chase analysis showed that Cln2p was synthesized as a 67-kDa precursor and processed to a 46-kDa mature protein (t(1/2) = 1 h). Subcellular fractionation analysis indicated that Cln2p is localized with cathepsin B in the high-density lysosomal fractions. Confocal immunomicroscopic analysis also revealed that Cln2p is colocalized with a lysosomal soluble marker, cathepsin D. The immunodepletion of Cln2p from normal fibroblast extracts caused a loss in the degradative capacity of subunit c, but not the beta subunit of ATP synthase, suggesting that the absence of Cln2p provokes the lysosomal accumulation of subunit c.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2573-82
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10349869-Aminopeptidases, pubmed-meshheading:10349869-Cell Line, pubmed-meshheading:10349869-DNA, Complementary, pubmed-meshheading:10349869-Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, pubmed-meshheading:10349869-Endopeptidases, pubmed-meshheading:10349869-Fibroblasts, pubmed-meshheading:10349869-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10349869-Heterozygote Detection, pubmed-meshheading:10349869-Humans, pubmed-meshheading:10349869-Kinetics, pubmed-meshheading:10349869-Lysosomes, pubmed-meshheading:10349869-Macromolecular Substances, pubmed-meshheading:10349869-Mitochondria, pubmed-meshheading:10349869-Neuronal Ceroid-Lipofuscinoses, pubmed-meshheading:10349869-Peptide Hydrolases, pubmed-meshheading:10349869-Proton-Translocating ATPases, pubmed-meshheading:10349869-RNA, Messenger, pubmed-meshheading:10349869-Reference Values, pubmed-meshheading:10349869-Serine Proteases, pubmed-meshheading:10349869-Skin, pubmed-meshheading:10349869-Transcription, Genetic
pubmed:year
1999
pubmed:articleTitle
A lysosomal proteinase, the late infantile neuronal ceroid lipofuscinosis gene (CLN2) product, is essential for degradation of a hydrophobic protein, the subunit c of ATP synthase.
pubmed:affiliation
Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't