Phosphatase Subfamily PPP4C

Phosphatase Classification: Fold MTDP: Superfamily MTDP: Family PPP: Subfamily PPP4C (catalytic subunit of PP4 holoenzyme)

Evolution

PPP4C is found in opisthokonta, amoebazoa and plants. Each of Drosophila melanogaster, C. elegans and monosiga has two PPP4Cs, which arose through different evolutionary events within individual lineages. For example, the second copy of Drosophila melanogaster CG11597 emerged in melanogaster group (see gOrtholog and Drosophila phylogeny).

Domain

PPP4C has a single domain - phosphatase domain.

Functions

PPP4C, catalytic subunit of Protein Phosphatase 4 (PP4) holoenzyme, is closely related to PPP2C, the catalytic subunit of PP2A holoenzyme. Like PP1 and PP2A, holoenzyme PP4 consists of the catalytic subunit and one or two regulatory subunits. At least 6 different holoenzyme complexes have been found.

Mammal PP4 participates in a number of processes essential for normal cellular physiology, including microtubule organization, homologous recombination (HR)-mediated DNA repair, the DNA damage response, histone modification, apoptosis, immunoglobulin (Ig) VDJ recombination, pre-TCR signaling, TNF signaling, Toll-like receptor (TLR)-4 signaling, and NF-κB regulation. Germline deletion of PP4 in mice is embryonic lethal, and conditional deletion of PP4 specifically in murine T cells severely impairs T cell development (see introduction in [1]).

PPP4C is implicated in cancer. For instance, high expression of PPP4C is associated with the aggressive malignant behavior of colorectal carcinoma [2].

PP4 dephoshorylate the phophorylated histone 2A variant, γ-H2AX, a marker for DNA damage and cell-cycle arrest. Interestingly, PP2A also dephosphorylates γ-H2AX.

PP4 in C. elegans is involved in M prophase, perhaps through dephosphorylate SUN-1 protein that is normally phosphorylated during the transition zone and early pachytene [3].

References

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