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Publication : Activated Ha-Ras but not TPA induces transcription through binding sites for activating transcription factor 3/Jun and a novel nuclear factor.

First Author  Nilsson M Year  1995
Journal  J Biol Chem Volume  270
Issue  20 Pages  12210-8
PubMed ID  7744871 Mgi Jnum  J:25520
Mgi Id  MGI:73236 Doi  10.1074/jbc.270.20.12210
Citation  Nilsson M, et al. (1995) Activated Ha-Ras but not TPA induces transcription through binding sites for activating transcription factor 3/Jun and a novel nuclear factor. J Biol Chem 270(20):12210-8
abstractText  We report the identification of a 20-base pair sequence mediating induced transcription in response to an activated Ha-ras gene and epidermal growth factor (EGF) but not 12-O-tetradecanoylphorbol-13-acetate stimulation. This signal-specific nuclear target is present in the long terminal repeat of a mouse VL30 retrotransposon expressed in epidermis. Functional studies and in vitro binding analyses using cultured keratinocytes (Balb/MK) reveal that the response element is composed of two cooperating sequence motifs in juxtaposed position, both of which are targets for induced binding activity 1-2 h after EGF stimulation. Of many different activating transcription factor/cAMP-responsive element binding protein/activating protein 1 factors tested, one part of the sequence selectively binds endogenous proteins immunologically related to activating transcription factor 3 (ATF3) and Jun isotypes. The other sequence is a target for a nuclear factor showing binding specificity unrelated to factors known to mediate EGF- or ras-induced transcription as determined by its sequence specificity and by antibody experiments. This component has been characterized and partially purified by gel filtration chromatography and velocity centrifugation revealing a Stokes radius of 43.6 A and a sedimentation coefficient of 9.7 S in solution. Based on these parameters, a molecular mass of 178,000 Da was calculated. The results indicate that the specific binding of ATF3/Jun and a previously uncharacterized factor account for signal-specific transcription in response to EGF or an activated Ha-ras gene in a cell type in which the cooperative action of an activated Ha-ras gene and 12-O-tetradecanoylphorbol-13-acetate cause tumor growth.
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