The Multifaceted Role of Protein Phosphatase 1 in Plasmodium. Issue 2 (February 2021)

• Record Type: Journal Article
• Authors: Khalife, Jamal; Fréville, Aline; Gnangnon, Bénédicte; Pierrot, Christine
• Is Part Of: Trends in parasitology. Volume 37:Issue 2(2021)
• Page Start: 154
• Page End: 164
• Publication Date: 2021-02
• Subjects: Plasmodium -- phosphatases -- PP1 -- regulatory subunits -- interactome -- proteomics; Parasitology -- Periodicals; Parasitology -- Periodicals; Biology -- Periodicals; Parasitology; Biology; Parasitologie -- Périodiques; Online resources; 571.999
• DOI: 10.1016/j.pt.2020.09.003
• Languages: English
• ISSNs: 1471-4922

Abstract

Abstract : Protein phosphatase type 1 (PP1) forms a wide range of Ser/Thr-specific phosphatase holoenzymes which contain one catalytic subunit (PP1c), present in all eukaryotic cells, associated with variable subunits known as regulatory proteins. It has recently been shown that regulators take a leading role in the organization and the control of PP1 functions. Many studies have addressed the role of these regulators in diverse organisms, including humans, and investigated their link to diseases. In this review we summarize recent advances on the role of PP1c in Plasmodium, its interactome and regulators. As a proof of concept, peptides interfering with the regulator binding capacity of PP1c were shown to inhibit the growth of P. falciparum, suggesting their potential as drug precursors. Highlights: In eukaryotes, protein dephosphorylation by protein phosphatase type 1 (PP1) holoenzymes is a major regulatory mechanism that is accomplished by the high combinatorial capacity of its conserved catalytic subunit (PP1c) with different PP1c-interacting proteins (PIPs) to control PP1 functions spatiotemporally. In Plasmodium, PP1c is essential for the completion of the intraerythrocytic development cycle (replication, egress) and interacts with conserved and Plasmodium -specific PIPs that are as essential as PP1c. Several Plasmodium PIPs belong to major protein complexes (proteasome, spliceosome, and ribosomal complex) that are crucial for parasite (sur)vival. The well known PP1 docking motif 'RVxF', expressed by PIPs, is a major contributor to their binding to Plasmodium PP1c and its functions.