A5023663301- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- FOXO transcription factor regulation
- Ubiquitin and proteasome pathways
- Metabolism, Diabetes, and Cancer
- Polyamine Metabolism and Applications
- Renal and related cancers
- Mast cells and histamine
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Vitamin C and Antioxidants Research
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Cancer, Hypoxia, and Metabolism
- Signaling Pathways in Disease
- Cancer Mechanisms and Therapy
- Vitamin D Research Studies
- RNA and protein synthesis mechanisms
- Growth Hormone and Insulin-like Growth Factors
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Genomics and Rare Diseases
Nazarbayev University
2019-2024
South Eastern Europe Telecommunications Academy
2024
The University of Texas MD Anderson Cancer Center
2011-2020
University of Houston
2011-2020
The University of Texas Health Science Center at Houston
2019
Whitehead Institute for Biomedical Research
2001-2010
Massachusetts Institute of Technology
2002-2010
Broad Institute
2005-2010
Howard Hughes Medical Institute
2010
McGill University
2001
Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis cancer and diabetes. Akt/PKB activation requires phosphorylation Thr308 loop by phosphoinositide-dependent 1 (PDK1) Ser473 within carboxyl-terminal hydrophobic motif an unknown kinase. We show that Drosophila human cells target rapamycin (TOR) its associated protein rictor are necessary for a reduction or mammalian TOR (mTOR) expression inhibited effector. The rictor-mTOR complex directly phosphorylated on vitro...
ONC201 triggers an apoptotic cellular stress response in both solid and blood tumors.
The raptor-mTOR protein complex is a key component of nutrient-sensitive signaling pathway that regulates cell size by controlling the accumulation cellular mass. How nutrients regulate through not well known. Here we show redox-sensitive mechanism phosphorylation effector S6K1, interaction between raptor and mTOR, kinase activity complex. In cells treated with oxidizing agents diamide or phenylarsine oxide, S6K1 increased became insensitive to nutrient deprivation. Conversely, reducing...
Cellular stress attenuates growth factor signaling through a phosphorylation event that blocks substrate access to the kinase complex mTORC2.
The PI3K-AKT pathway is hyperactivated in many human cancers, and several drugs to inhibit this pathway, including the PI3K/mTOR dual inhibitor NVP-BEZ235, are currently being tested various preclinical clinical trials. It has been shown that pharmacologic inhibition of results feedback activation other oncogenic signaling pathways, which likely will limit utilization these inhibitors cancer treatment. However, underlying mechanisms such regulation remain incompletely understood. a validated...
The FKBP-12-rapamycin associated protein (FRAP, also known as mTOR and RAFT-1) is a member of the phosphoinositide kinase related family. FRAP has serine/threonine activity mediates cellular response to mitogens through signaling p70s6 (p70 s6k ) 4E-BP1, resulting in an increase translation subsets mRNAs. Translational up-regulation blocked by inactivation rapamycin, G 1 cell cycle arrest. Rapamycin used immunosuppressant for kidney transplants currently under investigation antiproliferative...
The mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated cell cycle regulation and the DNA damage response. Its role tumor however, remains unclear. Here, we have shown that COP9 subunit 6 (CSN6) gene amplified human breast cancer specimens, CSN6 upregulated thyroid tumors. expression positively correlated with of murine double minute 2 (MDM2), potent negative regulator p53 suppressor. Expression appeared to...
HER2 overexpression drives Akt signaling and cell survival HER2-enriched breast tumors have a poor outcome when is upregulated. activated by phosphorylation at T308 via PI3K S473 mTORC2. The importance of PI3K-activated well documented in HER2-amplified cancer models, but the significance mTORC2-activated this setting remains uncertain. We report here that mTORC2 obligate cofactor Rictor enriched samples, correlating with increased on Akt. In invasive specimens, expression was upregulated...
The importance of the mTOR complex 2 (mTORC2) signaling in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 to drive formation, cell survival and resistance human epidermal growth factor receptor (HER2)-targeted therapy. Cell motility, a key step metastatic process, can be activated by mTORC2 luminal triple negative cancer lines, but its role promoting metastases from not yet clear.Because Rictor an obligate cofactor mTORC2, we...
In this report we show that extracellular signal-regulated kinase-1 and -2 (ERK-1 -2) respond differently to signals elicit proliferation and/or differentiation of myoblasts using the C2C12 cell line nondifferentiating mutant NFB4 cells derived from them. Induction by withdrawal serum rendered ERKs in relatively insensitive restimulation serum. Instead, myogenic was associated with sustained activation ERK-2 dependent on insulin-like growth factor II (IGF-II) autocrine loop. By contrast,...
In animal cells, growth factors coordinate cell proliferation and survival by regulating the phosphoinositide 3-kinase/Akt signaling pathway. Deregulation of this pathway is common in a variety human cancers. The PI3K-dependent kinase complex defined as mammalian target rapamycin 2 (mTORC2) functions regulatory Ser-473 Akt. We find that activation mTORC2 factor linked to specific phosphorylation its component rictor on Thr-1135. site induced stimulation expression oncogenic forms ras or...