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- Title
Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb.
- Authors
Rose, Nicola J.; Lever, Andrew M. L.
- Abstract
Background: Rapamycin is an immunosuppressive which represses translation of transcripts harbouring a polypyrimidine motif downstream of the mRNA cap site through the mammalian target of rapamycin complex. It inhibits the abnormal autologous proliferation of T-cell clones containing a transcriptionally active human T-lymphotropic virus, type I (HTLV-I) provirus, generated from infected subjects. We showed previously that this effect is independent of the polypyrimidine motifs in the viral long terminal repeat (LTR) R region suggesting that HTLV-I transcription, and not translation, is being affected. Here we studied whether rapamycin is having an effect on a specific transcription factor pathway. Further, we investigated whether mRNAs encoding transcription factors involved in HTLV-I transcriptional activation, specifically CREB, Ets and c-Myb, are implicated in the rapamycin-sensitivity of the HTLV-I LTR. Results: An in vitro analysis of the role of SRE- and NF-κB-mediated transcription highlighted the latter as rapamycin sensitive. Over-expression of c-Myb reversed the rapamycin effect. Conclusion: The sensitivity of HTLV-I transcription to rapamycin may be effected through an NF-κB-pathway associated with the rapamycin-sensitive mTORC1 cellular signalling network.
- Subjects
HTLV; RAPAMYCIN; RETROVIRUSES; MESSENGER RNA; TRANSCRIPTION factors; VIROLOGY
- Publication
Retrovirology, 2007, Vol 4, p24
- ISSN
1742-4690
- Publication type
Article
- DOI
10.1186/1742-4690-4-24