Linked Life Data

11241348

Source:http://linkedlifedata.com/resource/pubmed/id/11241348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-3-12
pubmed:abstractText
Aldolase B is an abundant cytosolic protein found in all eukaryotic cells. Like many glycolytic enzymes, this protein was sequestered into lysosomes for degradation during nutrient starvation. We report here that the degradation of recombinant aldolase B was enhanced two-fold when rat and human hepatoma cells were starved for amino acid and serum. In addition, starvation-induced degradation of aldolase B was inhibited by chloroquine, an inhibitor of lysosomal proteinases and by 3-methyladenine, an inhibitor of autophagy. Aldolase B has three lysosomal targeting motifs (Q(12)KKEL, Q(58)FREL, and IKLDQ(111)) that have been proposed to interact with hsc73 thereby initiating its transport into lysosomes. In this study, we have mutated the essential glutamine residues in each of these hsc73-binding motifs in order to evaluate their roles in the lysosomal degradation of aldolase B during starvation. We have found that when glutamines 12 or 58 are mutated to asparagines enhanced degradation of aldolase B proceeded normally. However, when glutamine 111 was mutated to an asparagine or a threonine, starvation-induced degradation was completely suppressed. These mutations did not appear to alter the tertiary structure of aldolase B since enzymatic activity was not affected. Our results suggest that starvation-induced lysosomal degradation of aldolase B requires both autophagy and glutamine 111. We discuss the possible roles for autophagy and hsc73-mediated transport in the lysosomal sequestration of aldolase B.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-58
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11241348-Amino Acid Motifs, pubmed-meshheading:11241348-Amino Acids, pubmed-meshheading:11241348-Animals, pubmed-meshheading:11241348-Autophagy, pubmed-meshheading:11241348-Base Sequence, pubmed-meshheading:11241348-Carcinoma, Hepatocellular, pubmed-meshheading:11241348-Culture Media, Serum-Free, pubmed-meshheading:11241348-Epitopes, pubmed-meshheading:11241348-Fructose-Bisphosphate Aldolase, pubmed-meshheading:11241348-Glutamine, pubmed-meshheading:11241348-HSC70 Heat-Shock Proteins, pubmed-meshheading:11241348-HSP70 Heat-Shock Proteins, pubmed-meshheading:11241348-Heat-Shock Proteins, pubmed-meshheading:11241348-Humans, pubmed-meshheading:11241348-Lysosomes, pubmed-meshheading:11241348-Molecular Chaperones, pubmed-meshheading:11241348-Molecular Sequence Data, pubmed-meshheading:11241348-Mutagenesis, Site-Directed, pubmed-meshheading:11241348-Protein Transport, pubmed-meshheading:11241348-Rats, pubmed-meshheading:11241348-Sequence Alignment, pubmed-meshheading:11241348-Signal Transduction, pubmed-meshheading:11241348-Transfection, pubmed-meshheading:11241348-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Starvation-induced lysosomal degradation of aldolase B requires glutamine 111 in a signal sequence for chaperone-mediated transport.
pubmed:affiliation
Department of Anatomy and Cell Biology, University of Florida College of Medicine, Health Science Center, P.O. Box 100235, Gainesville, FL 32610-0525, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.