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Mol Immunol. 2009 Aug;46(13):2694-8. doi: 10.1016/j.molimm.2009.05.185. Epub 2009 Jul 7.

Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation.

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  • 1Sidney-Kimmel Comprehensive Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.

Abstract

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved kinase which plays a role in integrating environmental cues. mTOR signals via two complexes: TORC1, which contains the Regulatory Associated Protein of TOR (raptor), and TORC2, which contains the Rapamycin-insensitive Companion of TOR (rictor). The immunosuppressive/anti-cancer agent rapamycin inhibits TORC1 function by disrupting the mTOR-raptor interaction. In an effort to understand the downstream consequences of TORC1 activation in T cells we performed a proteomic analysis of raptor binding proteins. Using this approach we have identified Hsp90 as an activation-induced binding partner of raptor in T cells. Pharmacologic inhibition of Hsp90 leads to a decrease in raptor expression and TORC1 activity. Furthermore, full T cell activation during Hsp90 blockade leads to T cell tolerance in the form of anergy. Overall, our findings suggest that Hsp90 inhibitors might represent a novel means of promoting T cell tolerance.

PMID:
19586661
PMCID:
PMC2768125
DOI:
10.1016/j.molimm.2009.05.185
[PubMed - indexed for MEDLINE]
Free PMC Article
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