FAM122A, a new endogenous inhibitor of protein phosphatase 2A

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Protein Phosphatase 2A (PP2A) is crucial for regulating fundamental cellular processes, including proliferation, transformation, and cell fate.
• Dysregulation of PP2A activity is implicated in various cellular dysfunctions and diseases.
• Identifying novel regulators of PP2A is essential for understanding its diverse roles.

Purpose of the Study:

• To investigate the interaction of the conserved protein FAM122A with PP2A.
• To determine the effect of FAM122A on PP2A phosphatase activity.
• To elucidate the role of FAM122A in cellular processes regulated by PP2A.

Main Methods:

• Co-immunoprecipitation assays to assess protein-protein interactions between FAM122A and PP2A subunits.
• In vitro phosphatase assays to measure the activity of PP2A complexes in the presence of FAM122A.
• Western blotting and ubiquitination assays to analyze PP2A-Cα degradation.
• Cell proliferation and colony formation assays to evaluate the impact of FAM122A on cell growth.

Main Results:

• FAM122A directly binds to PP2A-Aα and B55α subunits, but not B56α.
• FAM122A inhibits the phosphatase activity of the PP2A-Aα/B55α/Cα complex.
• FAM122A promotes the poly-ubiquitination and subsequent degradation of the PP2A catalytic subunit Cα.
• FAM122A silencing reduces cell growth and colony formation, while its overexpression enhances these processes.

Conclusions:

• FAM122A is identified as a novel endogenous inhibitor of PP2A.
• FAM122A regulates PP2A activity through direct interaction and promotion of catalytic subunit degradation.
• FAM122A plays a significant role in controlling cell proliferation and colony-forming ability.
• Further research is warranted to explore the physiological and pathophysiological implications of FAM122A as a PP2A inhibitor.