An alternatively spliced isoform of B-Myb is a transcriptional inhibitor.
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-Myb activity beside the known cyclin dependent mechanisms.
Horstmann
S
S
Institut für Biochemie, Westfälische-Wilhelms-Universität Münster, Germany.
Ferrari
S
S
Klempnauer
K H
KH
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D017124:Conserved Sequence; D019925:Cyclin A / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
D018797:Cell Cycle Proteins; D019925:Cyclin A; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D015534:Trans-Activators