Nucleophosmin/B23, a multifunctional protein that can regulate apoptosis.

Abstract:

: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.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Ye K

doi

10.4161/cbt.4.9.2072

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

918-23

issue

9

eissn

1538-4047

issn

1555-8576

pii

1148

journal_volume

4

pub_type

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