Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis

Area of Science:

• Molecular Biology
• Epigenetics
• Cellular Regulation

Background:

• Class IIa histone deacetylases (HDACs) are crucial transcriptional regulators in development.
• Their activity is controlled by phosphorylation-dependent nucleocytoplasmic shuttling, involving 14-3-3 proteins.
• The antagonistic protein phosphatase regulating this process remained unidentified.

Purpose of the Study:

• To identify the protein phosphatase responsible for dephosphorylating class IIa HDACs.
• To elucidate the regulatory mechanism of class IIa HDACs involving phosphatases and 14-3-3 proteins.
• To investigate the role of PP2A in controlling HDAC7-mediated functions.

Main Methods:

• Identification of PP2A as the phosphatase for class IIa HDACs.
• Investigation of the competitive binding between 14-3-3 proteins and PP2A.
• Utilized okadaic acid treatment and RNA interference to study HDAC7 regulation.

Main Results:

• PP2A was identified as the phosphatase that dephosphorylates 14-3-3 binding sites on class IIa HDACs.
• 14-3-3 protein association competitively inhibits PP2A-mediated dephosphorylation.
• PP2A constitutively dephosphorylates HDAC7, impacting T cell apoptosis and endothelial cell functions.

Conclusions:

• PP2A is the key antagonistic phosphatase regulating class IIa HDAC activity.
• A dynamic interplay between 14-3-3 proteins, kinases, and PP2A governs class IIa HDAC shuttling and function.
• This study provides a model for understanding class IIa HDAC regulation in biological processes.