The highly conserved DNA-binding domains of A-, B- and c-Myb differ with respect to DNA-binding, phosphorylation and redox properties

Abstract

In the Myb family, as in other families of transcription factors sharing similar DNA-binding domains (DBDs), diversity of function is believed to rely mainly on the less conserved parts of the proteins and on their distinct patterns of expression. However, small conserved differences between DBDs of individual members could play a role in fine-tuning their function. We have compared the highly conserved DBDs of the three vertebrate Myb proteins (A-, B- and c-Myb) and found distinct functional differences. While A- and c-Myb behaved virtually identically in a variety of DNA-binding assays, B-Myb formed complexes of comparatively lower stability, rapidly dissociating under competitive conditions and showing less tolerance to binding site variations. The three protein domains also differed as substrates for protein kinases. Whereas PKA in theory should target the DBDs of A- and c-Myb, but not B-Myb, only c-Myb was phosphorylated by PKA. CK2 phosphorylated all three proteins, although on different sites in the N-terminal region. Finally, B-Myb was remarkably sensitive to cysteine-directed oxidation compared to the other Myb proteins. Our data suggest that the small differences that have evolved between individual Myb family members lead to clear differences in DBD properties even if their sequence recognition remains the same.

Cis-regulatory analysis ofnodaland maternal control of dorsal-ventral axis formation by Univin, a TGF-β related to Vg1

“…In addition, we identified several binding sites for potential novel regulators of nodal expression including activating binding sites for homeodomain, Oct and bZIP factors, along with a binding site for a repressor, possibly Myb (Coffman et al, 1997). It is intriguing to note that several of the candidate transcription factors predicted to bind to this promoter are known to be regulated by redox signaling, including bZIP (Liu et al, 2005), Oct (Guo et al, 2004;Zheng et al, 2003) and Myb (Bergholtz et al, 2001;Brendeford et al, 1997;Myrset et al, 1993). In particular, a wealth of data is available on the role of bZIP transcription factors as sensors of redox signaling downstream of MAP kinases (Amoutzias et al, 2006;Liu et al, 2005).…”

c‐Maf interacts with c‐Myb to down‐regulate Bcl‐2 expression and increase apoptosis in peripheral CD4 cells

“…Potential MBS were identified based on the established consensus sequence YAACN(G/T) for Myb protein binding [52][53][54][55][56][57]. Five potential sites are located within the untranslated and coding regions of exon 2 (Fig.…”

Regulation of Nuclear Translocation of the Myb1 Transcription Factor by TvCyclophilin 1 in the Protozoan Parasite Trichomonas vaginalis

“…These Myb proteins share the conserved R2R3 DNA-binding domains (DBDs) 3 of the eukaryotic Myb protein family (19), but each has a variable N or C terminus that is much shorter than the variable C-terminal regulatory regions of vertebrate c-Myb, A-Myb, and B-Myb (20). Similar to c-Myb, the DBDs in Myb1, Myb2, and Myb3 are composed of six helices arranged in two bundles with two antiparallel ␤-sheets unique to Myb3 forming a small hairpin following the helices (21)(22)(23).…”