Protein phosphatase 2A (PP2A) is one of the most abundant serine-threonine phosphatases in mammalian cells. PP2A is a hetero-trimeric holoenzyme participating in a variety of physiological processes whose deregulation is often associated to cancer. The specificity and activity of this phosphatase is tightly modulated by a family of regulatory B subunits that dock the catalytic subunit to the substrates. Here we characterize a novel and unconventional molecular mechanism controlling the activity of the tumor suppressor PP2A. By applying a mass spectrometry-based interactomics approach, we identified novel PP2A interacting proteins. Unexpectedly we found that a significant number of RAB proteins associate with the PP2A scaffold subunit (PPP2R1A), but not with the catalytic subunit (PPP2CA). Such interactions occur in vitro and in vivo in specific subcellular compartments. Notably we demonstrated that one of these RAB proteins, RAB9, competes with the catalytic subunit PPP2CA in binding to PPP2R1A. This competitive association has an important role in controlling the PP2A catalytic activity, which is compromised in several solid tumors and leukemias.
Sacco, F., Mattioni, A., Boldt, K., Panni, S., Santonico, E., Castagnoli, L., et al. (2016). A subset of RAB proteins modulates PP2A phosphatase activity. SCIENTIFIC REPORTS, 6(1), 32857.
|Tipologia:||Articolo su rivista|
|Citazione:||Sacco, F., Mattioni, A., Boldt, K., Panni, S., Santonico, E., Castagnoli, L., et al. (2016). A subset of RAB proteins modulates PP2A phosphatase activity. SCIENTIFIC REPORTS, 6(1), 32857.|
|Settore Scientifico Disciplinare:||Settore BIO/18|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/srep32857|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||9-set-2016|
|Titolo:||A subset of RAB proteins modulates PP2A phosphatase activity|
|Autori:||Sacco, F; Mattioni, A; Boldt, K; Panni, S; Santonico, E; Castagnoli, L; Ueffing, M; Cesareni, G|
|Appare nelle tipologie:||01 - Articolo su rivista|