B-Myb and cyclin D1 mediate heat shock element dependent activation of the human HSP70 promoter.
Previous studies have shown that B-Myb, a conserved member of the Myb transcription factor family, is a potent activator of the promoter of the human HSP70 gene but does not activate promoters containing Myb binding sites. We have now investigated the transactivation properties of B-Myb in more detail. We here report that B-Myb activates the HSP70 promoter by a novel mechanism which involves the heat shock element (HSE). Deletion analysis of B-Myb shows that a specific domain in the center of B-Myb, but not the DNA-binding domain is required for HSE-dependent transactivation. We also show that deletion of the C-terminal domain of B-Myb does not affect HSE-dependent transactivation but allows the protein to activate a promoter containing Myb binding sites. This suggests that the ability to activate Myb binding site containing promoters is repressed in the context of full length B-Myb and that HSE dependent and Myb binding site dependent transactivation are distinct functions of B-Myb. Finally, we report that cyclin D1 like B-Myb strongly activates the HSP70 promoter via the HSE. HSE-dependent transactivation is a novel activity of cyclin D1 and appears to be independent of the phosphorylation of the Rb protein. Our results reveal an interesting and unexpected connection between HSE-dependent gene activation and proteins expressed during the G1/S-transition of the cell cycle.
Kamano
H
H
Hans-Spemann-Laboratory, Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Klempnauer
K H
KH
D001665:Binding Sites; D019938:Cyclin D1; D016213:Cyclins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D016193:G1 Phase / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D015513:Oncogene Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D016196:S Phase / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
D016213:Cyclins; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors; D019938:Cyclin D1