Phosphatase Subfamily PPP4C Functions

Phosphatase Classification: Fold PPPL: Superfamily PPPL: Family PPP: Subfamily PPP4C (catalytic subunit of PP4 holoenzyme) - Functions notes

Mammals

PP4 negatively regulates type I IFN Production and antiviral innate immunity by dephosphorylating and deactivating TANK-binding kinase 1 (TBK1) of TK group, ACK family according to KinBase classification [1]. Interferons bind to interferon receptors. All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains. Type I IFNs are found in all mammals, and homologous (similar) molecules have been found in birds, reptiles, amphibians and fish species. The mammalian types are designated IFN-α (alpha), IFN-β (beta), IFN-κ (kappa), IFN-δ (delta), IFN-ε (epsilon), IFN-τ (tau), IFN-ω (omega), and IFN-ζ (zeta, also known as limitin). Non-mammalian types are discussed at here.

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.

C. elegans

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].

Fungi

In budding yeast, the PP4 phosphatase has been shown to play a key role in preventing hyperactivation of the checkpoint kinase Rad53 [4].

References

1. Zhan Z, Cao H, Xie X, Yang L, Zhang P, Chen Y, Fan H, Liu Z, and Liu X. Phosphatase PP4 Negatively Regulates Type I IFN Production and Antiviral Innate Immunity by Dephosphorylating and Deactivating TBK1. J Immunol. 2015 Oct 15;195(8):3849-57. DOI:10.4049/jimmunol.1403083 |
2. Li X, Liang L, Huang L, Ma X, Li D, and Cai S. High expression of protein phosphatase 4 is associated with the aggressive malignant behavior of colorectal carcinoma. Mol Cancer. 2015 Apr 28;14:95. DOI:10.1186/s12943-015-0356-7 |
3. Sato-Carlton A, Li X, Crawley O, Testori S, Martinez-Perez E, Sugimoto A, and Carlton PM. Protein phosphatase 4 promotes chromosome pairing and synapsis, and contributes to maintaining crossover competence with increasing age. PLoS Genet. 2014 Oct;10(10):e1004638. DOI:10.1371/journal.pgen.1004638 |
4. Jablonowski CM, Cussiol JR, Oberly S, Yimit A, Balint A, Kim T, Zhang Z, Brown GW, and Smolka MB. Termination of Replication Stress Signaling via Concerted Action of the Slx4 Scaffold and the PP4 Phosphatase. Genetics. 2015 Nov;201(3):937-49. DOI:10.1534/genetics.115.181479 |
5. Chen MY, Chen YP, Wu MS, Yu GY, Lin WJ, Tan TH, and Su YW. PP4 is essential for germinal center formation and class switch recombination in mice. PLoS One. 2014;9(9):e107505. DOI:10.1371/journal.pone.0107505 |