TRB3 is a PI 3-kinase dependent indicator for nutrient starvation

Rolf Schwarzer; Sybille Dames; Daniel Tondera; Anke Klippel; Joerg Kaufmann

doi:10.1016/j.cellsig.2005.08.002

TRB3 is a PI 3-kinase dependent indicator for nutrient starvation

Cell Signal. 2006 Jun;18(6):899-909. doi: 10.1016/j.cellsig.2005.08.002. Epub 2005 Aug 29.

Authors

Rolf Schwarzer¹, Sybille Dames, Daniel Tondera, Anke Klippel, Joerg Kaufmann

Affiliation

¹ Atugen AG (SR Pharma plc subsidiary), Otto Warburg Haus (Nr. 80), Robert-Roessle-Strasse 10, 13125 Berlin, Germany. kaufmann@atugen.com

PMID: 16129579
DOI: 10.1016/j.cellsig.2005.08.002

Abstract

We have identified TRB3, a human homologue of Drosophila tribbles, as a novel transcriptional target of phosphatidylinositol (PI) 3-kinase. TRB3 expression is remarkably reduced in prostate cancer PC-3 cells after inhibition of PI 3-kinase. TRB3 expression is furthermore controlled by nutrient supplies: Both the lack of glucose or amino acids results in a substantial increase in TRB3 protein levels in a PI 3-kinase-dependent manner. This increase is reversed by the addition of fresh nutrients. Stress stimuli, such as osmotic stress, hypoxia or serum starvation do not affect TRB3 expression. Thus, TRB3 may function as a nutrient sensor. Inhibition of TRB3 expression has no effect on growth of PC-3 cells under regular growth conditions. However, in the absence of glucose overexpression of TRB3 in PC-3 cells can interfere with apoptosis and restore growth on extracellular matrix. Taken together, our data point to an important role of TRB3 in sensing reduced nutrient supplies and in providing survival signals during these periods.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids, Essential / deficiency*
Amino Acids, Essential / pharmacology
Cell Cycle Proteins / drug effects
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Line, Tumor
Cell Survival / drug effects
Cells, Cultured
Culture Media, Conditioned / chemistry
Culture Media, Conditioned / pharmacology
Glucose / deficiency*
Glucose / pharmacology
HeLa Cells
Humans
Male
Phosphatidylinositol 3-Kinases / metabolism*
Phosphatidylinositol 3-Kinases / pharmacology
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology
Protein Serine-Threonine Kinases / drug effects
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
RNA, Messenger / biosynthesis
Repressor Proteins / drug effects
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Signal Transduction
Transcriptional Activation

Substances

Amino Acids, Essential
Cell Cycle Proteins
Culture Media, Conditioned
RNA, Messenger
Repressor Proteins
TRIB3 protein, human
Protein Serine-Threonine Kinases
Glucose