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TRB3 is a PI 3-kinase dependent indicator for nutrient starvation
Rolf Schwarzer1, Sybille Dames, Daniel Tondera
1Atugen AG (SR Pharma plc subsidiary), Otto Warburg Haus (Nr. 80), Robert-Roessle-Strasse 10, 13125 Berlin, Germany. kaufmann@atugen.com
Cellular Signalling
|September 1, 2005
Summary
We identified TRB3 as a nutrient sensor regulated by phosphatidylinositol 3-kinase (PI 3-kinase). TRB3 protein levels increase when nutrients are scarce, helping cells survive by inhibiting apoptosis.
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- The phosphatidylinositol 3-kinase (PI 3-kinase) pathway is crucial for cell growth and survival.
- Understanding novel targets of PI 3-kinase is important for cancer research.
- The role of TRB3 in cellular response to nutrient availability is largely unknown.
Purpose of the Study:
- To identify novel transcriptional targets of PI 3-kinase.
- To investigate the role of TRB3 in cellular response to nutrient deprivation.
- To explore the function of TRB3 in prostate cancer cells.
Main Methods:
- Gene expression analysis to identify TRB3 as a PI 3-kinase target.
- Western blotting to assess TRB3 protein levels under various conditions.
- Cell culture experiments to study the effect of TRB3 on cell growth and apoptosis.
Main Results:
- TRB3 is a novel transcriptional target of PI 3-kinase, with its expression reduced upon PI 3-kinase inhibition.
- TRB3 protein levels significantly increase in the absence of glucose or amino acids in a PI 3-kinase-dependent manner.
- Overexpression of TRB3 in prostate cancer cells promotes survival by interfering with apoptosis and restoring growth on extracellular matrix during glucose deprivation.
Conclusions:
- TRB3 functions as a nutrient sensor, responding to reduced glucose and amino acid levels.
- TRB3 plays a critical role in providing survival signals under nutrient-scarce conditions.
- TRB3 represents a potential therapeutic target for enhancing cancer cell survival during metabolic stress.