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:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Pro47Ser variant of
p53
(S47) exists in African-descent populations and is associated with increased cancer risk in humans and mice. Due to impaired repression of the cystine importer
Slc7a11
, S47 cells show increased glutathione (GSH) accumulation compared to cells with wild -type
p53
. We show that mice containing the S47 variant display increased mTOR activity and oxidative metabolism, as well as larger size, improved metabolic efficiency, and signs of superior fitness. Mechanistically, we show that mTOR and its positive regulator Rheb display increased association in S47 cells; this is due to an altered redox state of
GAPDH
in S47 cells that inhibits its ability to bind and sequester Rheb. Compounds that decrease glutathione normalize
GAPDH
-Rheb complexes and mTOR activity in S47 cells. This study reveals a novel layer of regulation of mTOR by
p53
, and raises the possibility that this variant may have been selected for in early Africa.
...
PMID:Increased mTOR activity and metabolic efficiency in mouse and human cells containing the African-centric tumor-predisposing p53 variant Pro47Ser. 3317 Jul 74
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