Myc-interacting protein 1 target gene profile: a link to microtubules, extracellular signal-regulated kinase, and cell growth.
To study the role of the transcription factor Myc-interacting protein 1 (MIZ-1) in activating various target genes after induction with the microtubule disrupting agent T113242, we have used small interfering RNA duplexes (siRNAs) to knockdown the expression of MIZ-1. As expected, depletion of MIZ-1 resulted in the inhibition of T113242-dependent activation of the low-density lipoprotein receptor (LDLR) gene in hepatocytes. Cells transfected with MIZ-1 siRNAs also exhibited growth arrest. In addition, inhibition of the extracellular signal-regulated kinase (ERK) pathway inhibited T113242-induced nuclear accumulation of MIZ-1 and activation of LDLR. Gene expression microarray analysis under various induction conditions identified other T113242-activated genes affected by a decrease in MIZ-1 and inhibition of the ERK pathway. We also found that the accumulation of MIZ-1 in the nucleus is influenced by cell-cell contact and/or growth. Taken together, our studies suggest that MIZ-1 regulates a specific set of genes that includes LDLR and that the ERK pathway plays a role in the activation of target promoters by MIZ-1.
Ziegelbauer
Joseph
J
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Wei
Joyce
J
Tjian
Robert
R
D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C107961:ZBTB17 protein, human; D020928:Mitogen-Activated Protein Kinases