MAP/ERK kinase kinase 1 (MEKK1) mediates transcriptional repression by interacting with polycystic kidney disease-1 (PKD1) promoter-bound p53 tumor suppressor protein.

Détails

ID Serval
serval:BIB_A8DCC6118763
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
MAP/ERK kinase kinase 1 (MEKK1) mediates transcriptional repression by interacting with polycystic kidney disease-1 (PKD1) promoter-bound p53 tumor suppressor protein.
Périodique
Journal of Biological Chemistry
Auteur⸱e⸱s
Islam M.R., Jimenez T., Pelham C., Rodova M., Puri S., Magenheimer B.S., Maser R.L., Widmann C., Calvet J.P.
ISSN
1083-351X[electronic], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
285
Numéro
50
Pages
38818-38831
Langue
anglais
Résumé
Mitogen-activated protein kinase (MAPK) cascades regulate a wide variety of cellular processes that ultimately depend on changes in gene expression. We have found a novel mechanism whereby one of the key MAP3 kinases, Mekk1, regulates transcriptional activity through an interaction with p53. The tumor suppressor protein p53 down-regulates a number of genes, including the gene most frequently mutated in autosomal dominant polycystic kidney disease (PKD1). We have discovered that Mekk1 translocates to the nucleus and acts as a co-repressor with p53 to down-regulate PKD1 transcriptional activity. This repression does not require Mekk1 kinase activity, excluding the need for an Mekk1 phosphorylation cascade. However, this PKD1 repression can also be induced by the stress-pathway stimuli, including TNFα, suggesting that Mekk1 activation induces both JNK-dependent and JNK-independent pathways that target the PKD1 gene. An Mekk1-p53 interaction at the PKD1 promoter suggests a new mechanism by which abnormally elevated stress-pathway stimuli might directly down-regulate the PKD1 gene, possibly causing haploinsufficiency and cyst formation.
Mots-clé
Animals, Base Sequence, COS Cells, Cell Nucleus/metabolism, Cercopithecus aethiops, Gene Expression Regulation, Enzymologic, Humans, MAP Kinase Kinase Kinase 1/metabolism, Mice, Microscopy, Fluorescence/methods, Molecular Sequence Data, Mutagenesis, Oxidative Stress, Promoter Regions, Genetic, TRPP Cation Channels/metabolism, Transcription, Genetic, Tumor Necrosis Factor-alpha/metabolism, Tumor Suppressor Protein p53/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/02/2011 10:18
Dernière modification de la notice
20/08/2019 15:13
Données d'usage