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mTOR activation is a biomarker and a central pathway to autoimmune disorders,
cancer, obesity, and aging
#MMPMID25907074
Perl A
Ann N Y Acad Sci
2015[Jun]; 1346
(1
): 33-44
PMID25907074
show ga
The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine
kinase, which plays pivotal roles in integrating growth signals on a cellular
level. To support proliferation and survival under stress, two interacting
complexes that harbor mTOR, mTORC1 and mTORC2, promote the transcription of genes
involved in carbohydrate metabolism and lipogenesis, enhance protein translation,
and inhibit autophagy. Although rapamycin was originally developed as an
inhibitor of T cell proliferation for preventing organ transplant rejection, its
molecular target, mTOR, has been subsequently identified as a central regulator
of metabolic cues that drive lineage specification in the immune system. Owing to
oxidative stress, the activation of mTORC1 has emerged as a central pathway for
the pathogenesis of systemic lupus erythematosus and other autoimmune diseases.
Paradoxically, mTORC1 has also been identified as a mediator of the Warburg
effect that allows cell survival under hypoxia. Rapamycin and new classes of mTOR
inhibitors are being developed to block not only transplant rejection and
autoimmunity but also to treat obesity and various forms of cancer. Through
preventing these diseases, personalized mTOR blockade holds promise to extend
life span.
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