RRC ID 18128
Author Li H, Solomon E, Duhachek Muggy S, Sun D, Zolkiewska A.
Title Metalloprotease-disintegrin ADAM12 expression is regulated by Notch signaling via microRNA-29.
Journal J. Biol. Chem.
Abstract Metalloprotease-disintegrin ADAM12 is overexpressed and frequently mutated in breast cancer. We report here that ADAM12 expression in cultured mammalian cells is up-regulated by Notch signals. Expression of a constitutively active form of Notch1 in murine fibroblasts, myoblasts, or mammary epithelial cells or activation of the endogenous Notch signaling by co-culture with ligand-expressing cells increases ADAM12 protein and mRNA levels. Up-regulation of ADAM12 expression by Notch requires new transcription, is activated in a CSL-dependent manner, and is abolished upon inhibition of IκB kinase. Expression of a constitutively active Notch1 in NIH3T3 cells increases the stability of Adam12 mRNA. We further show that the microRNA-29 family, which has a predicted conserved site in the 3'-untranslated region of mouse Adam12, plays a critical role in mediating the stimulatory effect of Notch on ADAM12 expression. In human cells, Notch up-regulates the expression of the long form, but not the short form, of ADAM12 containing a divergent 3'-untranslated mRNA region. These studies uncover a novel paradigm in Notch signaling and establish Adam12 as a Notch-related gene.
Volume 286(24)
Pages 21500-10
Published 2011-6-17
DOI 10.1074/jbc.M110.207951
PII M110.207951
PMID 21518768
PMC PMC3122209
MeSH 3' Untranslated Regions ADAM Proteins / biosynthesis* ADAM12 Protein Animals CHO Cells Cricetinae Cricetulus Gene Expression Regulation* Humans Membrane Proteins / biosynthesis* Mice MicroRNAs / biosynthesis* Models, Biological NIH 3T3 Cells Peptide Hydrolases / metabolism Receptor, Notch1 / metabolism Receptors, Notch / metabolism* Signal Transduction Up-Regulation
IF 4.011
Times Cited 19
Human and Animal Cells OT11 (RCB1926) OT13 (RCB1927)