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Review
. 2020 Apr;53(4):181-190.
doi: 10.5483/BMBRep.2020.53.4.019.

Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe

Jaehong Park  1 , Dong-Hyun Lee  2
Affiliations
Review

Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe

Jaehong Park et al. BMB Rep. 2020 Apr.

Abstract

Protein phosphatase 4 (PP4), one of serine/threonine phosphatases, is involved in many critical cellular pathways, including DNA damage response (DNA repair, cell cycle regulation, and apoptosis), tumorigenesis, cell migration, immune response, stem cell development, glucose metabolism, and diabetes. PP4 has been steadily studied over the past decade about wide spectrum of physiological activities in cells. Given the many vital functions in cells, PP4 has great potential to develop into the finding of key working mechanisms and effective treatments for related diseases such as cancer and diabetes. In this review, we provide an overview of the cellular and molecular mechanisms by which PP4 impacts and also discuss the functional significance of it in cell health. [BMB Reports 2020; 53(4): 181-190].

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Classification of Ser/Thr phosphatase. Ser/Thr phosphatases are classified into phosphoprotein phosphatases (PPP) and Mg2＋-dependent protein phosphatase (PPM/PP2C). The PPP family can be further divided into seven subgroups: PP1, PP2A, PP2B, PP4, PP5, PP6, and PP7. Most Ser/Thr phosphatases are in the complex with their catalytic and regulatory subunits, except for PP5, PP7, and PP2C, which are solely comprised of catalytic subunits.
Fig. 2
Fig. 2
Protein phosphatase 4 complex and its inhibitory proteins. PP4 complex is comprised of its catalytic subunit (PP4C) and regulatory subunits (PP4R1, PP4R2, PP4R3α, PP4R3β, and PP4R4). PP4C interacts with PP4R1 or PP4R4 as a heterodimer, and PP4R2 and PP4R3α/β as a heterotrimer. Target substrates of PP4 complex to be dephosphorylated are determined via regulatory subunits. The activity of PP4 complexes can be regulated by the inhibitory proteins, including PP4IP, DHX38, and TIPRL. While PP4C/PP4R2/PP4R3α complex is regulated by PP4IP or DHX38, PP4C/PP4R2/PP4R3β complex is regulated by TIPRL or DHX38. Inhibitory proteins for PP4C/PP4R1 or PP4C/PP4R4 complex have not been elucidated. The reference numbers for the information are indicated. PP4IP, PP4 inhibitory protein; DHX38, DEAH box polypeptide 38; TIPRL, Tip41-like protein.
Fig. 3
Fig. 3
Multiple roles of protein phosphatase 4 in various cellular physiology. This schematic depicts the regions wherein PP4 participates and the genes regulated by or associated with PP4. The proteins in the closed boxes directly interact with PP4, but not all of them are targets to be dephosphorylated, whereas the proteins in the dashed boxes are indirectly regulated by PP4 or closely associated with the status of its expression. The organisms wherein the proteins are found and reference numbers are indicated; A, Arabidopsis thaliana; C, Caenorhabditis elegans; D, Drosophila melanogaster; H, human; M, mouse; N, Neurospora crassa; S, Saccharomyces cerevisiae; Sc, Schizosaccharomyces pombe; X, Xenopus laevis; Z, zebrafish.
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