PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ

Area of Science:

• Cell biology
• Molecular biology
• Biochemistry

Background:

• The Hippo pathway regulates organ size by controlling cell proliferation and apoptosis.
• TAZ acts as a transcriptional co-activator downstream of the Hippo pathway and is linked to cancer development.
• LATS kinase phosphorylates TAZ, inhibiting its function through cytoplasmic retention and degradation.

Purpose of the Study:

• To identify the phosphatase responsible for TAZ dephosphorylation.
• To elucidate the mechanism by which TAZ is dephosphorylated and its function is promoted.
• To understand the role of PP1 and ASPP2 in the Hippo-TAZ pathway.

Main Methods:

• Biochemical assays to identify TAZ phosphatase activity.
• In vitro and in vivo experiments to study TAZ phosphorylation and dephosphorylation.
• Analysis of protein-protein interactions between TAZ, PP1, and ASPP2.

Main Results:

• Protein phosphatase 1 (PP1) was identified as a TAZ phosphatase.
• PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promoting nuclear translocation and stability.
• ASPP2 facilitates TAZ-PP1 interaction, enhancing TAZ dephosphorylation and gene expression.

Conclusions:

• PP1A and ASPP2 are critical regulators of TAZ function.
• They antagonize LATS kinase activity by dephosphorylating TAZ.
• This mechanism promotes TAZ-dependent gene expression and influences organ size regulation.