title: KRAB-independent suppression of neoplastic cell growth by the novel zinc finger transcription factor KS1.
abstract: The study of zinc finger proteins has revealed their potential to act as oncogenes or tumor suppressors. Here we report the molecular, biochemical, and functional characterization of KS1 (KRAB/zinc finger suppressor protein 1), a novel, ubiquitously expressed zinc finger gene initially isolated from a rat pancreas library. KS1 contains 10 C2H2 zinc fingers, a KRAB-A/B motif, and an ID sequence that has been shown previously to participate in growth factor-regulated gene expression. Northern blot analysis using pancreatic cell lines demonstrates that KS1 mRNA is inducible by serum and epidermal growth factor, suggesting a role for this gene in cell growth regulation. Biochemical analysis reveals that KS1 is a nuclear protein containing two transcriptional repressor domains, R1 and R2. R1 corresponds to the KRAB-A motif, whereas R2 represents a novel sequence. Transformation assays using NIH3T3 cells demonstrate that KS1 suppresses transformation by the potent oncogenes Ha-ras, Galpha12, and Galpha13. Deletion of the R1/ KRAB-A domain does not modify the transformation suppressive activity of KS1, whereas deletion of R2 abolishes this function. Thus, KS1 is a novel growth factor-inducible zinc finger transcriptional repressor protein with the potential to protect against neoplastic transformation induced by several oncogenes.
authors.affiliation: Department of Molecular Neuroscience, Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: B
authors.initials: B
authors.lastname: Gebelein
authors.forename: M
authors.initials: M
authors.lastname: Fernandez-Zapico
authors.forename: M
authors.initials: M
authors.lastname: Imoto
authors.forename: R
authors.initials: R
authors.lastname: Urrutia
mesh_terms: D016475:3T3 Cells / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000737:chemistry; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015723:Gene Library; D005796:Genes; D016147:Genes, Tumor Suppressor; D016162:Genes, Wilms Tumor; D011905:Genes, ras; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000473:pathology; D011487:Protein Conformation; D051381:Rats; D012097:Repressor Proteins / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C116326:ZNF382 protein, human; C115768:ZNF85 protein, human; C485494:Zfp382 protein, rat; D004815:Epidermal Growth Factor