Methylation of PP2A and its role in transcriptional regulation

PPP2A (Proteins Phosphatase) is one of the most abundant phosphatases in cells. It consists of three subunits: A “scaffolding” subunit, C “catalytic” subunit and B “regulatory” subunit (which determines the function of PP2A). PP2A activity is influenced by the methylation occurring at Leucine 309 of the C subunit. LCMT1 (Leucin-methyltransferase 1) and PPME1 (Protein Phospho-methylesterase 1) are the proteins responsible for the methylation and demethylation of PP2A, respectively. Recently it has been shown that PP2A can be recruited to the chromatin by interacting with Integrator, a 15-subunit complex involved in RNA Polymerase II transcription regulation. PP2A, along with the kinase CDK9, is responsible for phosphorylation/dephosphorylation of the CTD of RNA Polymerase II, which determines the transition from pause-release to productive elongation. Although today we know how Integrator and PP2A interact with each other and how PP2A is recruited, we do not know yet when this binding occurs and how changes in PP2A methylation can affect RNA Polymerase II activity; hence, the main question to be addressed is: does the methylation status of PP2A affect transcription? How? Through a proteomic and genomic approach, I will try to convince you that yes, the methylation status of PP2A affects not only transcription but also some post-transcriptional events.