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An alternatively spliced isoform of B-Myb is a transcriptional inhibitor

Oncogene volume 19, pages 5428–5434 (2000)Cite this article

Abstract

B-Myb is a highly conserved member of the Myb transcription factor family. The primary transcript of the B-myb gene is spliced alternatively in two mRNAs which either contain or lack a sequence corresponding to the so-called exon 9A of c-myb. Recent studies showed that full-length B-Myb containing the exon 9A encoded amino acids is a cell cycle regulated transcription factor whose activity is stimulated by cyclin A/Cdk 2-dependent phosphorylation at the carboxyl-terminus of B-Myb. We have now investigated in more detail the transactivation potential of the shorter isoform of B-Myb lacking exon 9A. Here, we show that B-Myb lacking exon 9A has no transactivation activity even in the presence of cyclin A. This inactivity of the shorter isoform of B-Myb is not due an improper subcelluar localization. Our work suggests that B-Myb lacking exon 9A may act as an inhibitor for full-length B-Myb mediated transactivation. Furthermore, by analysing the transactivation potential of Gal4/B-Myb fusion proteins we have identified the amino-terminal part of the exon 9A as the principal transactivation domain of full-length B-Myb. The results presented here demonstrate that B-myb encodes both an activator and an inhibitor of transcription and, thus, reveal an additional level of regulation of B-Mybactivity beside the known cyclin dependent mechanisms.

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Acknowledgements

We thank Katja Wottrich for excellent technical assistance. This study was supported by a grant from the DFG (KL461/9-1) and by the Fonds der chemischen Industrie.

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Authors and Affiliations

  1. Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str.2, Münster, D-48149, Germany

    Sebastian Horstmann & Karl-Heinz Klempnauer

  2. Department of Oncology, Novartis Pharma AG, Klybeckstrasse 141, Basel, 4057, Switzerland

    Stefano Ferrari

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Horstmann, S., Ferrari, S. & Klempnauer, KH. An alternatively spliced isoform of B-Myb is a transcriptional inhibitor. Oncogene 19, 5428–5434 (2000). https://doi.org/10.1038/sj.onc.1203937

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