Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P30044 (
antioxidant enzyme
)
8,037
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Thioredoxin reductase 1 (TrxR1) is an important
antioxidant enzyme
that controls cellular redox homeostasis. By using a proteomic-based approach, here we identify TrxR1 as a caveolar membrane-resident protein. We show that
caveolin 1
, the structural protein component of caveolae, is a TrxR1-binding protein by demonstrating that the scaffolding domain of
caveolin 1
(amino acids 82-101) binds directly to the caveolin-binding motif (CBM) of TrxR1 (amino acids 454-463). We also show that overexpression of
caveolin 1
inhibits TrxR activity, whereas a lack of
caveolin 1
activates TrxR, both in vitro and in vivo. Expression of a peptide corresponding to the
caveolin 1
scaffolding domain is sufficient to inhibit TrxR activity. A TrxR1 mutant lacking the CBM, which fails to localize to caveolae and bind to
caveolin 1
, is constitutively active and inhibits oxidative-stress-mediated activation of the p53/p21(Waf1/Cip1) pathway and induction of premature senescence. Finally, we show that
caveolin 1
expression inhibits TrxR1-mediated cell transformation. Thus,
caveolin 1
links free radicals to activation of the p53/p21(Waf1/Cip1) pathway and induction of cellular senescence by acting as an endogenous inhibitor of TrxR1.
...
PMID:Inhibition of thioredoxin reductase 1 by caveolin 1 promotes stress-induced premature senescence. 1982 Jun 94
