KRAB-independent suppression of neoplastic cell growth by the novel zinc finger transcription factor KS1

Brian Gebelein, Martin Fernandez-Zapico, Mami Imoto, Raul Urrutia

Research output: Contribution to journalArticle

42 Scopus citations

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. KS 1 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, Gα12, and Gα13. 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.

Original languageEnglish (US)
Pages (from-to)1911-1919
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number11
DOIs
StatePublished - Dec 1 1998

Keywords

  • Epidermal growth factor
  • Exocrine pancreas
  • Kruppel-associated box
  • Neoplastic transformation
  • Zinc finger

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'KRAB-independent suppression of neoplastic cell growth by the novel zinc finger transcription factor KS1'. Together they form a unique fingerprint.

  • Cite this