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Akt regulates basic helix-loop-helix transcription factor-coactivator complex formation and activity during neuronal
Anne B Vojtek1, Jennifer Taylor, Stacy L DeRuiter
1Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Molecular and Cellular Biology
|June 17, 2003
Summary
Akt kinases promote neurogenesis by enhancing the function of neural basic helix-loop-helix (bHLH) transcription factors. Akt regulates bHLH protein complex formation and transcriptional activity, crucial for neuron generation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neural basic helix-loop-helix (bHLH) transcription factors are key regulators of neurogenesis in vertebrates.
- Peptide growth factor signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt, are critical for neuronal differentiation and survival.
Purpose of the Study:
- To investigate the role of Akt kinases in neurogenesis, specifically their impact on bHLH protein function.
- To determine if Akt's role in neurogenesis is separable from its function in cell survival.
Main Methods:
- RNA interference (RNAi) was used to reduce endogenous Akt1 and Akt2 expression.
- P19 cells were transfected with a neural bHLH expression vector.
- Caspase inhibitor z-VAD-FMK and PI3K/Akt inhibitor LY294002 were used to assess cell survival and Akt activity.
Main Results:
- Reduced Akt expression significantly decreased neuron generation, independent of cell death.
- Activated Akt1 enhanced complex formation between bHLH proteins and the coactivator p300.
- Akt activity augmented the transcriptional activity of neurogenin 3 with coactivators p300 or CBP.
Conclusions:
- Akt kinases play a crucial role in neuronal differentiation beyond cell survival.
- Akt regulates the assembly and activity of bHLH-coactivator complexes, promoting neurogenesis.