title: Negative autoregulation of c-Myb activity by homodimer formation through the leucine zipper.
abstract: The trans-activating and transforming capacities of the c-myb proto-oncogene product (c-Myb) are negatively regulated through a leucine zipper structure in its negative regulatory domain. We show here tht in cotransfection assays, maximal Myb-induced trans-activation occurs with relatively low amounts of wild-type c-Myb, while higher levels of c-Myb result in reduced Myb-induced trans-activation. By contrast, this apparent negative autoregulation is not observed with a c-Myb mutant containing an impaired leucine zipper. Data presented here suggest that this negative autoregulation of trans-activation by wild-type c-Myb is a consequence of homodimer formation by c-Myb through its leucine zipper and of the inability of c-Myb dimers to bind DNA. These findings point to a novel mechanism of regulation of a transcription factor.
authors.affiliation: Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: N
authors.initials: N
authors.lastname: Sakai
authors.forename: A
authors.initials: A
authors.lastname: Sarai
authors.forename: T
authors.initials: T
authors.lastname: Sudo
authors.forename: C
authors.initials: C
authors.lastname: Kanei-Ishii
authors.forename: R G
authors.initials: RG
authors.lastname: Ramsay
authors.forename: D
authors.initials: D
authors.lastname: Favier
authors.forename: T J
authors.initials: TJ
authors.lastname: Gonda
authors.forename: S
authors.initials: S
authors.lastname: Ishii
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D006706:Homeostasis; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D015533:Transcriptional Activation
chemical_list: D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D004247:DNA