Human A‐myb gene encodes a transcriptional activator containing the negative regulatory domains

Abstract

The myb gene family has three members, c-myb, A-myb, and B-myb. A-myb mRNA is mainly expressed in testis and peripheral blood leukocytes. A-Myb can activate transcription from the promoter containing Myb-binding sites in all cells examined. In addition to the two domains (a DNA-binding domain and a transcriptional activation domain), two negative regulatory domains have been identified in A-Myb. These results indicate that A-Myb functions as a transcriptional activator mainly in testis and peripheral blood cells, and the regulatory mechanism of A-Myb activity is similar to that of c-Myb.

Myb binding proteins: regulators and cohorts in transformation

“…The c-Myb protein has a well-characterized negative regulatory domain, and C-terminal truncation of cMyb, or the related A-Myb or B-Myb proteins, enhances transcriptional activity (Gonda et al, 1989a;GraÈ sser et al, 1991;Lane et al, 1997;Takahashi et al, 1995). In addition, overexpression of c-Myb is insu cient to e ciently transform cells in vitro or to induce tumors in animals (for review see .…”

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).…”

B-Myb and cyclin D1 mediate heat shock element dependent activation of the human HSP70 promoter

“…BMyb lacks homology to the transactivation domain conserved between c-Myb and A-Myb and its transactivation properties are strikingly di erent from those of c-Myb and A-Myb. In contrast to c-Myb and A-Myb, B-Myb does not e ciently transactivate promoters containing myb binding sites (Foos et al, 1992(Foos et al, , 1994Watson et al, 1993;Golay et al, 1994;Trauth et al, 1994;Takahashi et al, 1995). Transactivation by B-Myb has been observed in certain cell types and has been suggested to require cell-speci®c accessory proteins (Tashiro et al, 1995).…”