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.
Original language | English (US) |
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Pages (from-to) | 2694-2698 |
Number of pages | 5 |
Journal | Molecular Immunology |
Volume | 46 |
Issue number | 13 |
DOIs | |
State | Published - Aug 2009 |
Externally published | Yes |
Keywords
- Anergy
- Hsp90
- Rapamycin
- Raptor
- T cell
- mTOR
ASJC Scopus subject areas
- Immunology
- Molecular Biology