c-Myb-induced trans-activation mediated by heat shock elements without sequence-specific DNA binding of c-Myb

Chie Kanei-Ishii*, Takashi Yasukawa, Richard I. Morimoto, Shunsuke Ishii

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The c-myb proto-oncogene product (c-Myb) can transactivate the human hsp70 promoter in a transient cotransfection assay. The present studies have demonstrated that the heat shock element (HSE) in the hsp70 promoter mediates trans-activation by c-Myb. Mutagenesis of the DNA sequence in HSE indicated that the NGAAN motif is necessary for not only the heat shock response but also the c-Myb-induced trans-activation. The HSE in the hsp70 promoter does not contain a c-Myb-binding site, implying that the sequence-specific DNA binding of c-Myb is not required for the HSE-dependent trans-activation by c- Myb. We had demonstrated that a disruption of the leucine zipper motif in the central portion of the c-Myb molecule increased the degree of c-Myb-induced trans-activation of the promoter containing c-Myb-binding sites, suggesting that a putative inhibitor binds to c-Myb through this leucine zipper (Kanie- Ishii, C., MacMillan, E. M., Nomura, T., Sarai, A., Ramsay, R. G., Aimoto, S., Ishii, S., and Gonda, T. J. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3088-3092). However, disruption of the leucine zipper in c-Myb abolished the HSE-dependent trans-activation by c-Myb, whereas deletion of the transcriptional activation domain containing acidic amino acids in c-Myb did not abolish the HSE-dependent trans-activation by c-Myb. These results suggest that c-Myb can activate transcription of the gene containing HSEs by interacting with unidentified trans-acting factor(s) but not by a direct binding to the promoter through its DNA-binding domain.

Original languageEnglish (US)
Pages (from-to)15768-15775
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number22
StatePublished - Jun 3 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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