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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Format: | Article |
Language: | English |
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BMC
2007-04-01
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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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id | doaj.art-43149ca357754db5ba464181661a828e |
institution | Directory Open Access Journal |
issn | 1742-4690 |
language | English |
last_indexed | 2024-12-17T00:30:27Z |
publishDate | 2007-04-01 |
publisher | BMC |
record_format | Article |
series | Retrovirology |
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 |