Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb

<p>Abstract</p> <p>Background</p> <p>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 pro...

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Main Authors: Lever Andrew ML, Rose Nicola J
Format: Article
Language:English
Published: BMC 2007-04-01
Series:Retrovirology
Online Access:http://www.retrovirology.com/content/4/1/24
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author Lever Andrew ML
Rose Nicola J
author_facet Lever Andrew ML
Rose Nicola J
author_sort Lever Andrew ML
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>An <it>in vitro </it>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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-43149ca357754db5ba464181661a828e2022-12-21T22:10:20ZengBMCRetrovirology1742-46902007-04-01412410.1186/1742-4690-4-24Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-MybLever Andrew MLRose Nicola J<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>An <it>in vitro </it>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.</p> <p>Conclusion</p> <p>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.</p>http://www.retrovirology.com/content/4/1/24
spellingShingle Lever Andrew ML
Rose Nicola J
Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb
Retrovirology
title Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb
title_full Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb
title_fullStr Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb
title_full_unstemmed Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb
title_short Rapamycin-induced inhibition of HTLV-I LTR activity is rescued by c-Myb
title_sort rapamycin induced inhibition of htlv i ltr activity is rescued by c myb
url http://www.retrovirology.com/content/4/1/24
work_keys_str_mv AT leverandrewml rapamycininducedinhibitionofhtlviltractivityisrescuedbycmyb
AT rosenicolaj rapamycininducedinhibitionofhtlviltractivityisrescuedbycmyb