Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).

Triptolide (TPL), a key biologically active component of the Chinese medicinal herb Tripterygium wilfordii Hook. f., has potent anti-inflammation and anti-cancer activities. Its anti-proliferative and pro-apoptotic effects have been reported to be related to the inhibition of Nuclear Factor κB (NF-κ...

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Main Authors: Ying Wang, Jin-jian Lu, Li He, Qiang Yu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3172214?pdf=render
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spelling doaj-09c3d41ac4914475a3bc36bfdbef4d362020-11-24T21:26:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2399310.1371/journal.pone.0023993Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).Ying WangJin-jian LuLi HeQiang YuTriptolide (TPL), a key biologically active component of the Chinese medicinal herb Tripterygium wilfordii Hook. f., has potent anti-inflammation and anti-cancer activities. Its anti-proliferative and pro-apoptotic effects have been reported to be related to the inhibition of Nuclear Factor κB (NF-κB) and Nuclear Factor of Activated T-cells (NFAT) mediated transcription and suppression of HSP70 expression. The direct targets and precise mechanisms that are responsible for the gene expression inhibition, however, remain unknown. Here, we report that TPL inhibits global gene transcription by inducing proteasome-dependent degradation of the largest subunit of RNA polymerase II (Rpb1) in cancer cells. In the presence of proteosome inhibitor MG132, TPL treatment causes hyperphosphorylation of Rpb1 by activation of upstream protein kinases such as Positive Transcription Elongation Factor b (P-TEFb) in a time and dose dependent manner. Also, we observe that short time incubation of TPL with cancer cells induces DNA damage. In conclusion, we propose a new mechanism of how TPL works in killing cancer. TPL inhibits global transcription in cancer cells by induction of phosphorylation and subsequent proteasome-dependent degradation of Rpb1 resulting in global gene transcription, which may explain the high potency of TPL in killing cancer.http://europepmc.org/articles/PMC3172214?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Ying Wang
Jin-jian Lu
Li He
Qiang Yu
spellingShingle Ying Wang
Jin-jian Lu
Li He
Qiang Yu
Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).
PLoS ONE
author_facet Ying Wang
Jin-jian Lu
Li He
Qiang Yu
author_sort Ying Wang
title Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).
title_short Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).
title_full Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).
title_fullStr Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).
title_full_unstemmed Triptolide (TPL) inhibits global transcription by inducing proteasome-dependent degradation of RNA polymerase II (Pol II).
title_sort triptolide (tpl) inhibits global transcription by inducing proteasome-dependent degradation of rna polymerase ii (pol ii).
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description Triptolide (TPL), a key biologically active component of the Chinese medicinal herb Tripterygium wilfordii Hook. f., has potent anti-inflammation and anti-cancer activities. Its anti-proliferative and pro-apoptotic effects have been reported to be related to the inhibition of Nuclear Factor κB (NF-κB) and Nuclear Factor of Activated T-cells (NFAT) mediated transcription and suppression of HSP70 expression. The direct targets and precise mechanisms that are responsible for the gene expression inhibition, however, remain unknown. Here, we report that TPL inhibits global gene transcription by inducing proteasome-dependent degradation of the largest subunit of RNA polymerase II (Rpb1) in cancer cells. In the presence of proteosome inhibitor MG132, TPL treatment causes hyperphosphorylation of Rpb1 by activation of upstream protein kinases such as Positive Transcription Elongation Factor b (P-TEFb) in a time and dose dependent manner. Also, we observe that short time incubation of TPL with cancer cells induces DNA damage. In conclusion, we propose a new mechanism of how TPL works in killing cancer. TPL inhibits global transcription in cancer cells by induction of phosphorylation and subsequent proteasome-dependent degradation of Rpb1 resulting in global gene transcription, which may explain the high potency of TPL in killing cancer.
url http://europepmc.org/articles/PMC3172214?pdf=render
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AT lihe triptolidetplinhibitsglobaltranscriptionbyinducingproteasomedependentdegradationofrnapolymeraseiipolii
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