Protein phosphatase 4 catalytic subunit (PPP4C) (PP4)

Protein phosphatase 4 (PP4) is a highly conserved serine/threonine-protein phosphatase belonging to the phosphoprotein phosphatase (PPP) family (UniProt P60510). It primarily exists as a holoenzyme complex consisting of a catalytic subunit (PPP4C) and various regulatory subunits that determine its substrate specificity and subcellular localization (PubMed 12668731). PP4 plays a critical role in several essential cellular processes, including the DNA damage response, microtubule organization at centrosomes, and the regulation of signaling pathways such as NF-kappaB and TNF-alpha (PubMed 32139257). In the context of oncology, PP4 is frequently overexpressed in various malignancies, including breast, lung, and colorectal cancers, where it promotes tumor cell proliferation, migration, and resistance to apoptosis (PubMed 34964699). Its role in dephosphorylating key proteins like gamma-H2AX and 53BP1 makes it a vital regulator of genomic stability and DNA repair (PubMed 37309898). While specific clinical inhibitors are still in development, small molecules like fostriecin and cantharidin have demonstrated the therapeutic potential of targeting PP4 to sensitize cancer cells to DNA-damaging agents and induce mitotic slippage (PubMed 1.1.3). Additionally, PP4 has been implicated in metabolic disorders, such as hepatic insulin resistance, by modulating the JNK signaling pathway (PubMed 26673615). Targeting PP4 requires high specificity to avoid disrupting its essential roles in normal cellular homeostasis and genomic integrity.

Other names

PP-XPPXPPH3PPP4PPP4CSerine/threonine-protein phosphatase 4 catalytic subunit

Inhibition of the catalytic activity of the PP4 complex, leading to sustained phosphorylation of key substrates involved in DNA repair and cell cycle progression, which induces apoptosis and sensitizes cells to chemotherapy.