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Physiologic functions of PP2A: Lessons from genetically modified mice.

Sara Reynhout1, Veerle Janssens1

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|July 22, 2018
PubMed
Summary

Protein Phosphatase 2A (PP2A) is essential for life, with its regulatory subunits controlling diverse functions across tissues. Mouse models reveal PP2A

Keywords:
Cardiac dysfunctionGenetically modified mouse modelsHematopoiesis and immune system dysfunctionLipid and glucose metabolismProtein Phosphatase 2A (PP2A)TauopathyTumor suppressor

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Area of Science:

  • Biochemistry and Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • Protein Phosphatase 2A (PP2A) is a key Ser/Thr phosphatase family with catalytic, structural, and regulatory subunits.
  • The roles of PP2A's regulatory B-type subunits in substrate dephosphorylation and organismal function are not fully understood.
  • The mammalian PP2A system is complex, involving numerous subunit genes, assembly regulators, and inhibitors.

Purpose of the Study:

  • To review the physiological functions of PP2A across various tissues and developmental stages.
  • To synthesize findings from in vivo studies using PP2A mouse models.
  • To highlight the importance of PP2A subunits in organismal homeostasis and disease.

Main Methods:

  • Review of 63 PP2A transgenic, knockout, or knockin mouse models generated between 1998 and the present.
  • Analysis of data on PP2A's role in germ cell maturation, embryonic development, metabolic regulation, tumor suppression, and homeostasis in adult organs.
  • Synthesis of information on tissue-specific functions and functional redundancies of PP2A subunits.

Main Results:

  • PP2A is essential for survival in vivo.
  • PP2A plays critical roles in germ cell maturation, embryonic development, metabolic regulation, tumor suppression, and homeostasis of multiple adult organs.
  • Mouse models demonstrate tissue-specific functions and functional redundancies among PP2A subunits.

Conclusions:

  • PP2A is indispensable for a wide range of physiological processes.
  • Understanding PP2A subunit functions through mouse models is crucial for elucidating its role in health and disease.
  • Further characterization of existing and novel PP2A mouse models is vital for advancing PP2A (patho)physiology research and exploring therapeutic strategies.