Nucleophosmin/B23, a multifunctional protein that can regulate apoptosis.
Nucleophosmin (NPM)/B23, a multifunctional nucleolar protein, is overexpressed in actively proliferating cells and cancer cells. B23 is a tumor marker and exerts its oncogenic effect through binding and suppressing numerous tumor suppressors. NPM-ALK, an aberrant fusion protein produced from t(2;5) translocation in anaplastic large cell lymphoma (ALCL), fuses the N-terminus of B23 to the intracellular tyrosine kinase domain of ALK, provoking lymphomas by stimulating various mitogenic proteins including PI 3-kinase and PLC-gamma1. Overexpression of B23 inhibits apoptosis, while knockdown of B23 induces cell death. However, whether B23 is directly involved in blocking apoptotic machinery remains elusive. B23 is recently identified as a nuclear PI(3,4,5)P3 binding protein through a PI(3,4,5)P3 column and NGF-treated PC12 nuclear extracts. B23 has been shown to mediate the anti-apoptotic effects of NGF by inhibiting DNA fragmentation activity of CAD. B23 mutants that cannot associate with PI(3,4,5)P3 fail to prevent DNA fragmentation, indicating that PI(3,4,5)P3/B23 complex regulates the anti-apoptotic activity of NGF in the nucleus. Identification of a small molecule mediating the anti-apoptotic action of B23 unveils a novel therapeutic target for treatment of B23 amplified cancers.
Ye
Keqiang
K
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. kye@emory.edu
D000818:Animals; D017209:Apoptosis; D003851:Deoxyribonucleases / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D000090243:Nucleophosmin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*
D003851:Deoxyribonucleases; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; C000716967:NPM1 protein, human; C060974:phosphatidylinositol 3,4,5-triphosphate; C109663:caspase-activated deoxyribonuclease