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Medientyp:
E-Artikel
Titel:
Transcriptional activation by the Myb proteins requires a specific local promoter structure
Beteiligte:
Ganter, Brigitte;
Chao, Samuel T.;
Lipsick, Joseph S.
Erschienen:
Wiley, 1999
Erschienen in:
FEBS Letters, 460 (1999) 3, Seite 401-410
Sprache:
Englisch
DOI:
10.1016/s0014-5793(99)01373-3
ISSN:
1873-3468;
0014-5793
Entstehung:
Anmerkungen:
Beschreibung:
The biological effects of the cellular c‐Myb and the viral v‐Myb proteins are strikingly different. While c‐Myb is indispensable for normal hematopoiesis, v‐Myb induces acute leukemia. The v‐Myb DNA‐binding domain (DBD) differs from that of c‐Myb mainly by deletion of the first of three repeats which correlates with efficient oncogenic transformation and a decrease in DNA‐binding activity. To investigate the difference in DNA‐binding and transcriptional activation, oligonucleotide selection and electrophoretic mobility shift assays were employed. The v‐Myb DBD (R2R3) shows an intrinsic DNA‐binding specificity for an AT‐rich downstream extension of the Myb recognition element (MRE) PyAACT/GG for efficient binding to this site, whereas R1 within the c‐Myb DBD allows for more flexibility for this downstream extension. Therefore, due to the presence of repeat R1, c‐Myb can bind to a greater number of target sites. The intrinsic DNA‐binding specificity of R2R3 is further supported with the results from in vivo transcriptional activation experiments which demonstrated that both the v‐Myb and c‐Myb DBDs require an extension of the MRE (motif #1) by a downstream T‐stretch (motif #2) for full activity. Surprisingly, the T‐stretch improves binding when present on either strand, but is required on a specific strand for transcriptional activation.