Trans-activation by the c-mybproto-oncogene

Abstract

We present evidence that the mouse c-myb proto-oncogene encodes a transcriptional trans-activator. Trans-activation was assayed by cotransfection into CV1 monkey kidney cells of a c-myb cDNA expression plasmid together with a reporter plasmid carrying the chloramphenicol acetyltransferase (CAT) gene under the control of a test promoter and enhancer. Cotransfection with the c-myb cDNA plasmid caused a 20-fold stimulation of transcription from the promoter of the mouse alpha 2(I) collagen gene linked to tandem repeats of the simian virus 40 (SV40) enhancer element. Using different promoters in combination with varying numbers of repeats of the SV40 enhancer element, it was shown that tandem repeats of the SV40 enhancer mediated the c-myb-induced activation of transcription. These results show that the mouse c-myb gene product either is itself or induces, an activator of transcription that recognizes specific sequences in the SV40 enhancer.

Genes regulated by caloric restriction have unique roles within transcriptional networks

“…Four overrepresented transcription factor binding sites were present within the promoter regions of Serpinh1, Col3a1 and Col1a1 (Table 1). These binding sites were associated with numerous trans-acting elements, several of which are known to interact with collagen gene promoters, such as the myeloblastosis oncogene (Myb) (Nishina et al, 1989) and nuclear factor κB (NF-κB) (Rippe et al, 1999). Serphinh1, Col3a1 and Col1a1 were co-expressed with several other genes downregulated by CR in four of the tissue types considered by Swindell (2008), including Col5a2 (collagen, type V, alpha 2), Col1a2 (collagen, type I, alpha 2), Fbn1 (fibrillin 1) and Sparc (secreted acidic cysteine rich glycoprotein) (Supplemental Data File 3).…”

B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein truncation

“…DNA-binding is mediated through a comparatively large aminoterminal domain (Howe et al, 1990;Oehler et al, 1990) which demonstrates a high degree of conservation within this protein family. All three members of the Myb protein family have been reported to activate transcription from responsive promoters (Nishina et al, 1989;Weston and Bishop, 1989;Mizuguchi et al, 1990;Foos et al, 1994;Golay et al, 1994;Ma and Calabretta, 1994;Takahashi et al, 1995), however, there are distinct di erences in their transcription regulatory properties, particularly between c-Myb and B-Myb. Transactivation by c-Myb requires only the DNA binding domain and a weakly acidic region (amino acids 275 ± 325) which is conserved in A-Myb but not in B-Myb (Sakura et al, 1989;Weston and Bishop, 1989).…”

Oncogenic activation of c-Myb by carboxyl-terminal truncation leads to decreased proteolysis by the ubiquitin-26S proteasome pathway

“…The DNA binding region, responsible for sequence-speci®c binding to DNA, resides in the amino-terminal part of the protein and comprises three imperfect repeats R1, R2 and R3 (Klempnauer and Sippel, 1987;Biedenkapp et al, 1988;Sakura et al, 1989;Howe et al, 1990). The fact that the centrally located TA domain is hydrophilic and slightly acidic (Nishina et al, 1989;Weston and Bishop, 1989;Ibanez and Lipsick, 1990) places cMyb in a large class of transcription factors that have a similar weakly de®ned structure. Its transactivation activity can be modulated by a large NRD at the carboxyl-terminus (Sakura et al, 1989, Kalkbrenner et al, 1990, although de®ned components within the NRD, such as the leucine zipper structure and a phosphorylation site at S528, have also been implicated individually in the negative regulation of this function (Hu et al, 1991;Kanei-Ishii et al, 1992;Aziz et al, 1995).…”