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HTLV-1 HBZ cooperates with JunD to enhance transcription of the human telomerase reverse transcriptase gene (hTERT)
- Source :
- Retrovirology, Vol 4, Iss 1, p 92 (2007)
- Publication Year :
- 2007
- Publisher :
- BMC, 2007.
-
Abstract
- Abstract Background Activation of telomerase is a critical and late event in tumor progression. Thus, in patients with adult-T cell leukaemia (ATL), an HTLV-1 (Human T cell Leukaemia virus type 1)-associated disease, leukemic cells display a high telomerase activity, mainly through transcriptional up-regulation of the human telomerase catalytic subunit (hTERT). The HBZ (HTLV-1 bZIP) protein coded by the minus strand of HTLV-1 genome and expressed in ATL cells has been shown to increase the transcriptional activity of JunD, an AP-1 protein. The presence of several AP-1 binding sites in the hTERT promoter led us to investigate whether HBZ regulates hTERT gene transcription. Results Here, we demonstrate using co-transfection assays that HBZ in association with JunD activates the hTERT promoter. Interestingly, the -378/+1 proximal region, which does not contain any AP-1 site was found to be responsible for this activation. Furthermore, an increase of hTERT transcripts was observed in cells co-expressing HBZ and JunD. Chromatin immunoprecipitation (ChIP) assays revealed that HBZ, and JunD coexist in the same DNA-protein complex at the proximal region of hTERT promoter. Finally, we provide evidence that HBZ/JunD heterodimers interact with Sp1 transcription factors and that activation of hTERT transcription by these heterodimers is mediated through GC-rich binding sites for Sp1 present in the proximal sequences of the hTERT promoter. Conclusion These observations establish for the first time that HBZ by intervening in the re-activation of telomerase, may contribute to the development and maintenance of the leukemic process.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 17424690
- Volume :
- 4
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Retrovirology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.1ea25b04da540acbf1bf836fd02005a
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/1742-4690-4-92