Transcriptional control by myb oncogene product.
Structure and function of two domains of c-Myb were analyzed. We show that a leucine zipper structure is a component of the negative regulatory domain, because its disruption markedly increases both the transactivating and transforming capacities of c-Myb. Our results suggest that an inhibitor which suppresses transactivation binds to c-Myb through the leucine zipper, and that c-Myb can be oncogenically activated by mis-sense mutation. We also proposed a model, the "tryptophan cluster", for the structure of the Myb DNA-binding domain, in which the three tryptophans form a cluster in the hydrophobic core in each repeat. The results of NMR analysis of repeat 3 revealed that the conserved tryptophans play a key role to make the hydrophobic core.
Ishii
S
S
Laboratory of Molecular Genetics, Tsukuba Life Science Center, Ibaraki, Japan.
Nomura
T
T
Kanei-Ishii
C
C
Nakagoshi
H
H
Sudo
T
T
Sawazaki
T
T
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005809:Genes, Regulator; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D012995:Solubility; D014158:Transcription, Genetic; D014364:Tryptophan / Q000032:analysis* / Q000737:chemistry; D014867:Water / Q000737:chemistry
D004268:DNA-Binding Proteins; D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic; D014867:Water; D014364:Tryptophan