The Krüppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact.
Zf9/CPBP/KLF6 is a widely expressed member of the Krüppel-like family of transcriptional factors which regulates gene expression in hepatic stellate cells. Because of its ubiquitous expression including in the esophagus, we have explored its function in the esophageal squamous epithelium, a model system to study cellular proliferation and differentiation. Reverse transcription-PCR (RT-PCR) and Western blot analyses revealed that Zf9 was highly expressed in human esophageal squamous cancer cell lines. Additionally, Zf9 localizes to the esophageal squamous epithelium by immunohistochemistry. Using transient transfection, Zf9 transactivates the human keratin 4 (K4) promoter reporter gene construct in a subset of the esophageal cancer cell lines through indirect mechanisms. Co-transfection of Zf9 and GKLF/KLF4, which is also a member of the Krüppel-like factors and expressed in the esophageal squamous epithelium, leads to coactivation in an additive fashion. Furthermore, we demonstrate that there is a physical interaction between GKLF and Zf9, a novel finding for Krüppel-like family members.
Okano
J
J
Division of Gastroenterology, University of Pennsylvania, 415 Curie Blvd., Philadelphia, PA 19104-6144, USA.
Opitz
O G
OG
Nakagawa
H
H
Jenkins
T D
TD
Friedman
S L
SL
Rustgi
A K
AK
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D004947:Esophagus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000235:genetics*; D000090062:Kruppel-Like Factor 4; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D008970:Molecular Weight; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000715467:KLF4 protein, human; C105465:KLF6 protein, human; D000090062:Kruppel-Like Factor 4; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D007633:Keratins