Phosphorylation and transcriptional activity regulation of retinoid-related orphan receptor alpha 1 by protein...

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Retinoid-related orphan receptor alpha1 (RORalpha1) is crucial for neuronal survival, particularly in the cerebellum, and regulates reactive oxygen species homeostasis.
• RORalpha1's constitutive activity suggests complex regulatory mechanisms, potentially involving post-translational modifications.
• Protein kinase C (PKC) is implicated in neuronal survival and differentiation, hinting at a role in RORalpha1 regulation.

Purpose of the Study:

• To investigate the involvement of Protein Kinase C (PKC) in the regulation of Retinoid-related orphan receptor alpha1 (RORalpha1) transcriptional activity.
• To determine if PKC mediates post-translational modifications of RORalpha1.
• To explore the role of mitogen-activated protein kinase/extracellular signal-regulated kinase (1/2) in this regulatory pathway.

Main Methods:

• Over-expression of human RORalpha1 in cortical neurons and COS-7 cells.
• Treatment of cells with effectors targeting PKC activity.
• Analysis of RORalpha1 phosphorylation and transcriptional activity.
• Investigation of mitogen-activated protein kinase/extracellular signal-regulated kinase (1/2) involvement.

Main Results:

• Conventional PKCs were shown to induce phosphorylation of RORalpha1.
• PKC activation resulted in the inhibition of RORalpha1 transcriptional activity.
• Evidence suggests a role for MAPK/ERK (1/2) in this inhibitory mechanism.

Conclusions:

• Conventional PKCs directly regulate RORalpha1 activity through phosphorylation and inhibition.
• These findings provide novel insights into the post-translational control of RORalpha1.
• Understanding RORalpha1 regulation is critical for elucidating mechanisms of neuronal cell death in neurodegenerative diseases.