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Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics

Mónica Ferreira1, Monique Beullens1, Mathieu Bollen1

  • 1Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, B-3000 Leuven, Belgium.

Biochimica Et Biophysica Acta. Molecular Cell Research
|July 30, 2018
PubMed

Insights

Protein Phosphatase 1 (PP1) and its regulatory partners control cellular dephosphorylation. Mouse models reveal PP1 complexes are crucial in human diseases, highlighting new therapeutic targets.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Protein Phosphatase 1 (PP1) is a key enzyme in mammalian cells, responsible for over half of all phosphoserine/threonine dephosphorylation.
  • PP1 functions as part of diverse holoenzymes, formed by association with regulatory PP1-interacting proteins (PIPs), each targeting specific substrates.

Purpose of the Study:

  • To explore the link between PP1, PIPs, and human disease phenotypes using genetically engineered mouse models.
  • To identify novel therapeutic targets for PP1-related diseases through structural reverse genetics.

Main Methods:

  • Literature screening for genetically engineered mouse models of PP1 isoforms and 104 PIPs.
  • Analysis of disease-associated phenotypes linked to PP1 and PIPs in mouse models.

Main Results:

  • Mouse models were identified for all PP1 isoforms and 104 PIPs.
  • PP1 and 49 PIPs were associated with human disease phenotypes.
  • Phenotypes for 17 PIPs were directly linked to altered PP1 function, with 32 PIPs lacking this information.

Conclusions:

  • PP1 holoenzymes play a pleiotropic role in both health and disease.
  • Structural reverse genetics offers a promising approach to discover new therapeutic targets for PP1-related disorders.
Keywords:
PP1 interacting proteins (PIP)Protein phosphatase 1human disease-associated phenotypesmouse geneticsstructural reverse genetics

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