All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase.
Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase involved in the regulation of many cellular processes. A confirmed tumor suppressor protein, PP2A is genetically altered or functionally inactivated in many cancers highlighting a need for its therapeutic reactivation. In this review we discuss recent literature on PP2A: the elucidation of its structure and the functions of its subunits, and the identification of molecular lesions and post-translational modifications leading to its dysregulation in cancer. A final section will discuss the proteins and small molecules that modulate PP2A and how these might be used to target dysregulated forms of PP2A to treat cancers and other diseases.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Jaya
J
Sangodkar
Department of Medicine and Institute for Transformative Molecular Medicine, Case Western Reserve University, Cleveland, OH, USA.
Caroline C
CC
Farrington
Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Kimberly
K
McClinch
Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Matthew D
MD
Galsky
Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
David B
DB
Kastrinsky
Department of Medicine and Institute for Transformative Molecular Medicine, Case Western Reserve University, Cleveland, OH, USA.
Goutham
G
Narla
D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D021122:Protein Subunits; D025521:Tumor Suppressor Proteins; D054648:Protein Phosphatase 2
CIP2A; PP2A; SET; cancer; cancer biology; cell signaling; drug development; protein phosphatases; structural biology; tumor suppressors