Linked Life Data

15893727

Source:http://linkedlifedata.com/resource/pubmed/id/15893727

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-5-16
pubmed:abstractText
Phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P(3)] is an essential second messenger implicated in various cellular processes. Cytoplasmic PI(3,4,5)P(3) has been well characterized, but little is known about the physiological role of nuclear PI(3,4,5)P(3). Here, we describe a nuclear PI(3,4,5)P(3) receptor, nucleophosmin (NPM)/B23, that mediates the antiapoptotic effects of NGF by inhibiting DNA fragmentation activity of caspase-activated DNase (CAD). Employing PI(3,4,5)P(3) column and NGF-treated PC12 nuclear extracts, we identified B23 as a nuclear PI(3,4,5)P(3) binding protein. Purification from nuclear extract demonstrates that B23 contributes to DNA fragmentation inhibitory activity. Depletion of B23 from nuclear extracts or knockdown B23 in PC12 cells abolishes NGF-provoked protective effect, whereas overexpression of B23 in PC12 cells prevents apoptosis. Further, hydrolyzing PI(3,4,5)P(3) with PTEN or SHIP abrogates its antiapoptotic activity. Moreover, B23 mutants that can not associate with PI(3,4,5)P(3) fail to prevent DNA fragmentation. Thus, the nuclear B23-PI(3,4,5)P(3) complex regulates the antiapoptotic activity of NGF in the nucleus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1097-2765
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
435-45
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Nucleophosmin/B23, a nuclear PI(3,4,5)P(3) receptor, mediates the antiapoptotic actions of NGF by inhibiting CAD.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural