RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas

Arunthathi Thiagalingam, Andrée De Bustros, Michael Borges, Rajani Jasti, Debra Compton, Lara Diamond, Mack Mabry, Douglas W. Ball, Stephen B. Baylin, Barry D. Nelkin

Research output: Contribution to journalArticlepeer-review

Abstract

An activated ras oncogene induces a program of differentiation in the human medullary thyroid cancer cell line TT. This differentiation process is accompanied by a marked increase in the transcription of the human calcitonin (CT) gene. We have localized a unique Ras-responsive transcriptional element (RRE) in the CT gene promoter. DNase I protection indicates two domains of protein-DNA interaction, and each domain separately can confer Ras-mediated transcriptional inducibility. This bipartite RRE was also found to be Raf responsive. By affinity screening, we have cloned a cDNA coding for a zinc finger transcription factor (RREB-1) that binds to the distal RRE. The consensus binding site for this factor is CCCCAAACCACCCC. RREB-1 is expressed ubiquitously in human tissues outside the adult brain. Overexpression of RREB-1 protein in TT cells confers the ability to mediate increased transactivation of the CT gene promoter-reporter construct during Ras- or Raf-induced differentiation. These data suggest that RREB-1 may play a role in Ras and Raf signal transduction in medullary thyroid cancer and other cells.

Original languageEnglish (US)
Pages (from-to)5335-5345
Number of pages11
JournalMolecular and cellular biology
Volume16
Issue number10
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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