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and
NOTCH
(Received for publication, December 13, 1996)
,
From the Within the human ERBB-2 gene
promoter, a 100-base pair region 5
Department of Medicine, University of
California San Diego, La Jolla, California 92093-0650 and
§ The Salk Institute, La Jolla, California 92037
to the TATA box enhances basal
transcription 200-fold. Two palindromes present within this 100-base
pair region are important for transcription. The palindrome binding
protein was purified to homogeneity and found to be identical to
RBPJ
, the mammalian homolog of Drosophila Suppressor of Hairless
(Su(H)). Recombinant RBPJ bound the ERBB-2 promoter with
affinity comparable with that seen with well characterized RBPJ
binding sites. RBPJ activated an ERBB-2
palindrome-containing promoter in 293 cells. Because in
Drosophila Su(H) acts downstream of NOTCH and because
NOTCH·Su(H)/RBPJ stimulates transcription from target promoters,
NOTCH-IC, a constitutively active form of NOTCH, was tested for effects
on the ERBB-2 palindrome. NOTCH-IC further increased
RBPJ-mediated transcription on wild type but not mutant
ERBB-2 palindrome. Thus, RBPJ can activate ERBB-2 transcription and serve as an anchor to mediate
NOTCH function on the ERBB-2 gene.
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