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Regulation of Telomerase Expression and Activity by AP‐1 Transcription Factors
Author(s) -
Bhandarkar Vinaya Vittal,
Marable Jennifer,
Gollahon Lauren,
Pfarr Curt
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb72-d
Subject(s) - telomerase , telomerase reverse transcriptase , chromatin immunoprecipitation , transcription factor , microbiology and biotechnology , transcription (linguistics) , promoter , biology , gene expression , chemistry , gene , genetics , linguistics , philosophy
Telomerase is a specialized reverse transcriptase associated with >85% of human cancers and is considered a hallmark of transformation. Telomerase activity is absent in most normal cells, with a low basal activity present in certain regenerative tissues. Expression of the catalytic component (hTERT) is the limiting factor for telomerase activity while the template RNA (hTR) is constitutively expressed in most cells. As the hTERT promoter contains four putative AP‐1 binding sites, hTERT is a candidate AP‐1 responsive gene. The AP‐1 transcription factor, consisting of dimers formed between Jun and Fos proteins, helps to regulate differentiation, growth and apoptosis. We are examining the influence of AP‐1 proteins on hTERT transcription and telomerase activity in both transformed and non‐transformed human cell lines. Following overexpression of select Jun or Fos proteins, binding of AP‐1 complexes to the hTERT promoter will be followed by gel‐shift analysis (EMSA) and chromatin immunoprecipitation assays (ChIP) and hTERT promoter activity will be examined using synthetic luciferase reporter constructs. AP‐1 regulation of hTERT mRNA and protein expression will also be determined. Finally, the effect of AP‐1 on telomerase activity will be followed using the Telomeric Repeat Amplification Protocol (TRAP) assay. These experiments will help clarify how AP‐1 can regulate hTERT expression and thereby telomerase activity. This research is funded by the American Cancer Society.