Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-3-7
pubmed:abstractText
Regulation of the synthesis, function and degradation of HDM2 (Mdm2 in mouse) plays a key role in controlling the abundance and activity of the transcription factor p53, with consequent implications for the proliferation and survival of normal and cancer cells. We have previously identified the regulation of export of HDM2 mRNA from the nucleus as a novel point of control of HDM2 synthesis. This process is dependent on the activity of the growth factor-regulated MAP-kinase kinases (MEKs). Here, we provide evidence that the eIF4E kinase MNK1 is a key downstream effector of MEKs in this regulatory pathway. We show that HDM2 mRNA export in breast cancer cells is promoted by overexpressed eIF4E in a MEK- and MNK1-dependent manner, and inhibition of MNK1 suppresses endogenous HDM2 mRNA export pathways. This MNK1- and eIF4E-dependent HDM2 regulation occurs through sequences in the 3' untranslated region of HDM2 mRNA, and consequently HDM2 mRNA transcripts from both the constitutive P1 and inducible P2 promoters are regulated by this pathway. eIF4E is a known oncogene that is overexpressed in human tumours, including the majority of breast cancers. This pathway, therefore, may play an important role in the dysregulation of HDM2 oncoprotein expression that occurs in many human tumours.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3' Untranslated Regions, http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-4E, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/MDM2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/MKNK1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase..., http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1645-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17828301-3' Untranslated Regions, pubmed-meshheading:17828301-Active Transport, Cell Nucleus, pubmed-meshheading:17828301-Breast Neoplasms, pubmed-meshheading:17828301-Cell Line, Tumor, pubmed-meshheading:17828301-Cell Nucleus, pubmed-meshheading:17828301-Cytoplasm, pubmed-meshheading:17828301-Eukaryotic Initiation Factor-4E, pubmed-meshheading:17828301-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17828301-Humans, pubmed-meshheading:17828301-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17828301-Luciferases, pubmed-meshheading:17828301-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:17828301-Phosphorylation, pubmed-meshheading:17828301-Promoter Regions, Genetic, pubmed-meshheading:17828301-Protein-Serine-Threonine Kinases, pubmed-meshheading:17828301-Proto-Oncogene Proteins c-mdm2, pubmed-meshheading:17828301-RNA, Messenger, pubmed-meshheading:17828301-Signal Transduction, pubmed-meshheading:17828301-Tumor Suppressor Protein p53
pubmed:year
2008
pubmed:articleTitle
MNK1 and EIF4E are downstream effectors of MEKs in the regulation of the nuclear export of HDM2 mRNA.
pubmed:affiliation
Cancer Sciences Division, University of Southampton, Southampton General Hospital, Southampton, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't