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.

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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