Cellular inhibitors of Protein Phosphatase PP2A in cancer

Protein Phosphatases of type 2A (PP2A) represent a major class of structurally complex Ser/Thr phosphatases, which have recently gained a lot of interest in cancer biology because of their establishment as genuine tumor suppressors. PP2A phosphatases comprise a large family of >80 holoenzymes with complex structure, pleiotropic functions and diverse ways to regulate their biological activities. PP2A catalytic activity can be directly inhibited by an emerging set of specific cellular PP2A inhibitory proteins, including Acidic Nuclear Phosphoprotein 32a (ANP32a), Suvar 3-9/Enhancer of zeste/Trithorax (SET), Cancerous Inhibitor of PP2A (CIP2A), members of the cAMP-Regulated PhosphoProtein/a-Endosulfin (ARPP-16/19/ENSA) family, and Type 2A Interacting Protein (TIP). In addition, the PP2A Methyl Esterase 1 (PME-1), a regulator of reversible carboxy-terminal methylation of the PP2A catalytic C subunit, stabilizes an inactive PP2A C conformation and may be considered as an atypical inhibitor. Although sometimes poorly understood at the molecular level, these inhibitors either directly bind to the PP2A catalytic subunit or target very specific PP2A holoenzymes. In a wide variety of cancers, cellular PP2A inhibitors are aberrantly expressed, sometimes with very high frequency, and this constitutes a major mechanism by which the tumor suppressive function of PP2A can be impaired within a tumor. This offers interesting perspectives for therapeutic interference and some promising pre-clinical studies will be discussed.

Jaar van publicatie:2012

BOF-keylabel:ja

IOF-keylabel:ja

BOF-publication weight:0.1

CSS-citation score:1

Authors from:Higher Education

Toegankelijkheid:Closed