Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2010-9-2
pubmed:abstractText
Cell transformation by the v-rel oncogene is mediated by the aberrant expression of genes that are normally tightly regulated by other Rel/NF-kappaB family members. Although a number of genes inappropriately activated or suppressed by v-Rel have been identified, their contributions to the v-Rel transformation process have been poorly characterized. Here, we examine the role of individual AP-1 proteins in v-Rel-mediated transformation. v-Rel-transformed cells exhibit elevated RNA and protein expression of c-Fos, c-Jun and ATF2 and sustained repression of Fra-2. c-Fos and c-Jun are essential in both the initiation and maintenance of v-Rel-mediated transformation, whereas Fra-2 is dispensable. By employing a c-Jun dimerization mutant, we further identified Fos/Jun heterodimers as major contributors to the v-Rel transformation process. The inability of c-Rel to induce the expression of c-Fos and c-Jun contributes to its weaker oncogenic potential relative to v-Rel. Our studies also demonstrate that v-Rel may induce AP-1 members by directly upregulating gene expression (c-fos and ATF2) and by activating pathways that stimulate AP-1 activity. Although elevated expression of ATF2 is also required for v-Rel-mediated transformation, its ectopic overexpression is inhibitory. Investigating the mode of ATF2 regulation revealed a positive feedback mechanism whereby ATF2 induces p38 MAPK phosphorylation to further induce its own activity. In addition, these studies identified Ha-Ras as an effector of v-Rel-mediated transformation and reveal a novel role for ATF2 in the inhibition of the Ras-Raf-MEK-ERK signaling pathway. Overall, these studies reveal distinct and complex roles of AP-1 proteins in Rel/NF-kappaB oncogenesis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-10602460, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-10602467, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-10602468, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-10696433, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-10712905, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-10801448, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-10962557, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-11402340, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-11447113, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-11533227, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-11967310, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-12145210, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-12483529, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-14585353, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-1495981, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-15304344, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-15314185, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-15564374, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-15920551, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-16050133, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-16123212, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-16186799, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-16369914, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-16574096, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-17072331, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-17189429, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-17699753, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-18227516, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-1827203, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-18348191, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-19377508, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-20060892, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-3034432, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-3142689, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-6312449, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-7600582, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-8254742, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-8361768, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-8527134, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-9069263, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-9205096, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-9209405, http://linkedlifedata.com/resource/pubmed/commentcorrection/20562914-9566919
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 2, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP..., http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase..., http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins v-rel, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins p21(ras), http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1, http://linkedlifedata.com/resource/pubmed/chemical/raf Kinases
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4925-37
pubmed:dateRevised
2011-7-25
pubmed:meshHeading
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