The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades.
Exon trapping and cDNA selection procedures were used to search for novel genes at human chromosome 11p13, a region previously associated with loss of heterozygosity in epithelial carcinomas. Using these approaches, we found the ESE-2 and ESE-3 genes, coding for ETS domain-containing transcription factors. These genes lie in close proximity to the catalase gene within a approximately 200-kilobase genomic interval. ESE-3 mRNA is widely expressed in human tissues with high epithelial content, and immunohistochemical analysis with a newly generated monoclonal antibody revealed that ESE-3 is a nuclear protein expressed exclusively in differentiated epithelial cells and that it is absent in the epithelial carcinomas tested. In transient transfections, ESE-3 behaves as a repressor of the Ras- or phorbol ester-induced transcriptional activation of a subset of promoters that contain ETS and AP-1 binding sites. ESE-3-mediated repression is sequence- and context-dependent and depends both on the presence of high affinity ESE-3 binding sites in combination with AP-1 cis-elements and the arrangement of these sites within a given promoter. We propose that ESE-3 might be an important determinant in the control of epithelial differentiation, as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades.
Tugores
A
A
Axys Pharmaceuticals, Inc., South San Francisco, CA 94080, USA. autogores@yahoo.com
Le
J
J
Sorokina
I
I
Snijders
A J
AJ
Duyao
M
M
Reddy
P S
PS
Carlee
L
L
Ronshaugen
M
M
Mushegian
A
A
Watanaskul
T
T
Chu
S
S
Buckler
A
A
Emtage
S
S
McCormick
M K
MK
D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D004247:DNA; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D010802:Phylogeny; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C403306:EHF protein, human; C112442:Ehf protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA