PMID- 10639150
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 97
IP  - 2
DP  - 2000 Jan 18
TI  - Enzymatic reduction of disulfide bonds in lysosomes: characterization of a
      gamma-interferon-inducible lysosomal thiol reductase (GILT).
PG  - 745-50
AB  - Proteins internalized into the endocytic pathway are usually degraded. Efficient 
      proteolysis requires denaturation, induced by acidic conditions within lysosomes,
      and reduction of inter- and intrachain disulfide bonds. Cytosolic reduction is
      mediated enzymatically by thioredoxin, but the mechanism of lysosomal reduction
      is unknown. We describe here a lysosomal thiol reductase optimally active at low 
      pH and capable of catalyzing disulfide bond reduction both in vivo and in vitro. 
      The active site, determined by mutagenesis, consists of a pair of cysteine
      residues separated by two amino acids, similar to other enzymes of the
      thioredoxin family. The enzyme is a soluble glycoprotein that is synthesized as a
      precursor. After delivery into the endosomal/lysosomal system by the mannose
      6-phosphate receptor, N- and C-terminal prosequences are removed. The enzyme is
      expressed constitutively in antigen-presenting cells and induced by IFN-gamma in 
      other cell types, suggesting a potentially important role in antigen processing.
FAU - Arunachalam, B
AU  - Arunachalam B
AD  - Section of Immunobiology, Howard Hughes Medical Institute, Yale University School
      of Medicine, P.O. Box 208011, New Haven, CT 06520-8011, USA.
FAU - Phan, U T
AU  - Phan UT
FAU - Geuze, H J
AU  - Geuze HJ
FAU - Cresswell, P
AU  - Cresswell P
LA  - eng
SI  - GENBANK/AF097362
GR  - R01 AI023081/AI/NIAID NIH HHS/United States
GR  - R37 AI023081/AI/NIAID NIH HHS/United States
GR  - AI23081/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA, Complementary)
RN  - 0 (Disulfides)
RN  - 0 (Mannosephosphates)
RN  - 3672-15-9 (mannose-6-phosphate)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.8.4.2 (Protein Disulfide Reductase (Glutathione))
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - COS Cells
MH  - DNA, Complementary/chemistry/genetics
MH  - Disulfides/*metabolism
MH  - Endosomes/enzymology/ultrastructure
MH  - Enzyme Induction/drug effects
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Interferon-gamma/pharmacology
MH  - Lysosomes/*enzymology
MH  - Mannosephosphates/metabolism
MH  - Microscopy, Immunoelectron
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Oxidation-Reduction
MH  - Protein Disulfide Reductase (Glutathione)/biosynthesis/genetics/metabolism
MH  - Protein Processing, Post-Translational
MH  - Sequence Analysis, DNA
MH  - Tumor Cells, Cultured/drug effects/enzymology/ultrastructure
PMC - PMC15401
EDAT- 2000/01/19 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/01/19 09:00
PHST- 2000/01/19 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/01/19 09:00 [entrez]
AID - 10.1073/pnas.97.2.745 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):745-50. doi: 10.1073/pnas.97.2.745.