Linked Life Data

10646503

Source:http://linkedlifedata.com/resource/pubmed/id/10646503

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-2-10
pubmed:abstractText
Nerve growth factor (NGF) activates the transcription factors nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1) in sympathetic neurons. Whereas NGF-inducible NF-kappaB is required for the survival of neurons, c-Jun has the ability to promote neuronal death. In this report, we have examined the effect of NGF withdrawal on c-Jun and NF-kappaB transcription factors in PC12 cells differentiated to a neuronal phenotype. We show that the withdrawal of NGF from these cultures results in de novo synthesis of c-Jun, increase in AP-1 activity, and down-regulation of NF-kappaB activity. To investigate how the signal transduction pathways activating c-Jun and NF-kappaB are differentially regulated by NGF, we performed transcriptional analyses. Expression of ReIA (NF-kappaB) suppressed the c-Jun-dependent transcription of c-jun, and this effect was reversed by overexpression of the coactivator p300. RelA's effects on c-Jun transcription were mediated by competitive binding of the carboxy-terminal region of RelA to the CH1 domain of p300, which also binds to c-Jun; deletion of this region abrogated the ability of RelA to inhibit c-Jun activity. Furthermore, the inhibition of endogenous NF-kappaB in NGF-maintained neuronal PC12 cells led to the induction of c-Jun synthesis and a marked increase in cell death. Together, these studies demonstrate a functional interaction between NF-kappaB and c-Jun and suggest a novel mechanism of NF-kappaB-mediated neuroprotection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
527-39
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Functional interplay between nuclear factor-kappaB and c-Jun integrated by coactivator p300 determines the survival of nerve growth factor-dependent PC12 cells.
pubmed:affiliation
Department of Microbiology and Immunology, University of Rochester Medical Center, New York 14642, USA. sanjay_maggirwar@urmc.rochester.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't