AI Article Synopsis
- An activated ras oncogene triggers differentiation in human medullary thyroid cancer cells, leading to increased transcription of the calcitonin (CT) gene.
- Researchers identified a specific Ras-responsive transcriptional element (RRE) in the CT gene promoter that is involved in Ras-mediated transcription regulation.
- The study also discovered a zinc finger transcription factor, RREB-1, which binds to the RRE and enhances CT gene transcription when overexpressed in cancer cells during Ras or Raf signaling.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC231532 | PMC |
| http://dx.doi.org/10.1128/MCB.16.10.5335 | DOI Listing |
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