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2000
Volume 5, Issue 7
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Reflecting its critical role in integrating cell growth and division with the cellular nutritional environment, the mammalian target of rapamycin *(mTOR) is a highly conserved downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B) signaling pathway. mTOR activates both the 40S ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 4E-binding protein-1. As a consequence of inhibiting its downstream messengers, mTOR inhibitors prevent cyclindependent kinase (CDK) activation, inhibit retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help cause GI phase arrest. Constitutive activation of the PI3K/Akt kinases occur in human leukemias. FLT3, VEGF, and BCR-ABL mediate their activities via mTOR. New rapamycin analogs including CCI- 779, RAD001, and AP23573, are entering clinical studies for patients with hematologic malignancies.

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/content/journals/cmm/10.2174/156652405774641034
2005-11-01
2025-05-21
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/content/journals/cmm/10.2174/156652405774641034
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  • Article Type:
    Review Article
Keyword(s): AKT; AP23573; CCI-779; leukemia; mTOR; phosphatidylinositol 3' kinase; RAD001
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