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Nucleic Acids Research, 1994, Vol. 22, No. 13 2466-2475
© 1994


MOLECULAR BIOLOGY

The carboxyterminus of human c-myb protein stimulates activated transcription in trans

Gerd Vorbrueggen, Frank Kalkbrenner+, Stephan Guehmann and Karin Moelling*

Max-Planck-Institut für Molekulare Genetik Abteilung Schuster, Ihnestrasse 73, D-14195 Berlin, Germany

* To whom correspondence should be addressed at: Institut für Medizinische Virologie.Universität Zürich, CH-8028 Zürich, Switzerland

Received April 25, 1994. Revised June 8, 1994. Accepted June 8, 1994.

The cellular c-myb gene encodes a transcription factor composed of a DNA-binding domain, a transactivating domain and a regulatory domain located at its carboxy (C-) terminus. The latter one is deleted in the transforming viral protein v-Myb. Here we show that deletion of the C-terminus of c-Myb increases the transcriptional transactivation activity of c-Myb defining it as cis-acting negative regulatory domain. Cotransfection of the Cterminus in an in vivo competition assay causes stimulation of the transcriptional activity of various vand c-Myb expression constructs in trans. The effect is dose-dependent and independent of the kind of DNAbinding domain, since c-Myb as well as GAL4-c-Myb chimaeras can be stimulated in trans. Other transcription factors, such as GAL4-VP16, GAL4, c-Jun or C/EBPß are also stimulated by the cotransfected Cterminus. In contrast, human B-Myb is not stimulated by the c-Myb C-terminus in trans. The data suggest that the C-terminus of c-Myb may interact with a cellular inhibitor which is part of the protein complex mediating activated transcription and may stimulate in trans by sequestering away such an inhibitor. Binding of c-Myb to a putative inhibitor would explain differences between c-Myb in comparison to B- and v-Myb in transcriptional regulation.


+Present address: Institut für Pharmakologie der Freien Universität Berlin, Thielallee 69/73, D-14195 Berlin, Germany


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