SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells
Identifieur interne : 000057 ( Main/Merge ); précédent : 000056; suivant : 000058SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells
Auteurs : Liang-Jun Wang ; Jing-Ting Chiou ; Yuan-Chin Lee ; Chia-Hui Huang ; Yi-Jun Shi ; Long-Sen ChangSource :
- Journal of Cellular and Molecular Medicine [ 1582-1838 ] ; 2020.
Abstract
The contribution of vincristine (VCR)‐induced microtubule destabilization to evoke apoptosis in cancer cells remains to be resolved. Thus, we investigated the cytotoxic mechanism of VCR on U937 and HL‐60 human leukaemia cell lines. We discovered that VCR treatment resulted in the up‐regulation of TNF‐α expression and activation of the death receptor pathway, which evoked apoptosis of U937 cells. Moreover, VCR induced microtubule destabilization and mitotic arrest. VCR treatment down‐regulated SIRT3, and such down‐regulation caused mitochondrial ROS to initiate phosphorylation of p38 MAPK. p38 MAPK suppressed MID1‐modulated degradation of the protein phosphatase 2A (PP2A) catalytic subunit. The SIRT3‐ROS‐p38 MAPK‐PP2A axis inhibited tristetraprolin (TTP)‐controlled TNF‐α mRNA degradation, consequently, up‐regulating TNF‐α expression. Restoration of SIRT3 and TTP expression, or inhibition of the ROS‐p38 MAPK axis increased the survival of VCR‐treated cells and repressed TNF‐α up‐regulation. In contrast to suppression of the ROS‐p38 MAPK axis, overexpression of SIRT3 modestly inhibited the effect of VCR on microtubule destabilization and mitotic arrest in U937 cells. Apoptosis of HL‐60 cells, similarly, went through the same pathway. Collectively, our data indicate that the SIRT3‐ROS‐p38 MAPK‐PP2A‐TTP axis modulates TNF‐α expression, which triggers apoptosis of VCR‐treated U937 and HL‐60 cells. We also demonstrate that the apoptotic signalling is not affected by VCR‐elicited microtubule destabilization.
Url:
DOI: 10.1111/jcmm.14949
PubMed: 31930676
PubMed Central: 7028858
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000659
- to stream Pmc, to step Curation: 000659
- to stream Pmc, to step Checkpoint: 000052
- to stream Ncbi, to step Merge: 000E25
- to stream Ncbi, to step Curation: 000E25
- to stream Ncbi, to step Checkpoint: 000E25
Links to Exploration step
PMC:7028858Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells</title>
<author><name sortKey="Wang, Liang Un" sort="Wang, Liang Un" uniqKey="Wang L" first="Liang-Jun" last="Wang">Liang-Jun Wang</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chiou, Jing Ing" sort="Chiou, Jing Ing" uniqKey="Chiou J" first="Jing-Ting" last="Chiou">Jing-Ting Chiou</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lee, Yuan Hin" sort="Lee, Yuan Hin" uniqKey="Lee Y" first="Yuan-Chin" last="Lee">Yuan-Chin Lee</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huang, Chia Ui" sort="Huang, Chia Ui" uniqKey="Huang C" first="Chia-Hui" last="Huang">Chia-Hui Huang</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shi, Yi Un" sort="Shi, Yi Un" uniqKey="Shi Y" first="Yi-Jun" last="Shi">Yi-Jun Shi</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chang, Long En" sort="Chang, Long En" uniqKey="Chang L" first="Long-Sen" last="Chang">Long-Sen Chang</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="jcmm14949-aff-0002"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">31930676</idno>
<idno type="pmc">7028858</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028858</idno>
<idno type="RBID">PMC:7028858</idno>
<idno type="doi">10.1111/jcmm.14949</idno>
<date when="2020">2020</date>
<idno type="wicri:Area/Pmc/Corpus">000659</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000659</idno>
<idno type="wicri:Area/Pmc/Curation">000659</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000659</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000052</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000052</idno>
<idno type="wicri:Area/Ncbi/Merge">000E25</idno>
<idno type="wicri:Area/Ncbi/Curation">000E25</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000E25</idno>
<idno type="wicri:doubleKey">1582-1838:2020:Wang L:sirt:pp:a</idno>
<idno type="wicri:Area/Main/Merge">000057</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells</title>
<author><name sortKey="Wang, Liang Un" sort="Wang, Liang Un" uniqKey="Wang L" first="Liang-Jun" last="Wang">Liang-Jun Wang</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chiou, Jing Ing" sort="Chiou, Jing Ing" uniqKey="Chiou J" first="Jing-Ting" last="Chiou">Jing-Ting Chiou</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lee, Yuan Hin" sort="Lee, Yuan Hin" uniqKey="Lee Y" first="Yuan-Chin" last="Lee">Yuan-Chin Lee</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huang, Chia Ui" sort="Huang, Chia Ui" uniqKey="Huang C" first="Chia-Hui" last="Huang">Chia-Hui Huang</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Shi, Yi Un" sort="Shi, Yi Un" uniqKey="Shi Y" first="Yi-Jun" last="Shi">Yi-Jun Shi</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chang, Long En" sort="Chang, Long En" uniqKey="Chang L" first="Long-Sen" last="Chang">Long-Sen Chang</name>
<affiliation><nlm:aff id="jcmm14949-aff-0001"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="jcmm14949-aff-0002"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Cellular and Molecular Medicine</title>
<idno type="ISSN">1582-1838</idno>
<idno type="eISSN">1582-4934</idno>
<imprint><date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>The contribution of vincristine (VCR)‐induced microtubule destabilization to evoke apoptosis in cancer cells remains to be resolved. Thus, we investigated the cytotoxic mechanism of VCR on U937 and HL‐60 human leukaemia cell lines. We discovered that VCR treatment resulted in the up‐regulation of TNF‐α expression and activation of the death receptor pathway, which evoked apoptosis of U937 cells. Moreover, VCR induced microtubule destabilization and mitotic arrest. VCR treatment down‐regulated SIRT3, and such down‐regulation caused mitochondrial ROS to initiate phosphorylation of p38 MAPK. p38 MAPK suppressed MID1‐modulated degradation of the protein phosphatase 2A (PP2A) catalytic subunit. The SIRT3‐ROS‐p38 MAPK‐PP2A axis inhibited tristetraprolin (TTP)‐controlled TNF‐α mRNA degradation, consequently, up‐regulating TNF‐α expression. Restoration of SIRT3 and TTP expression, or inhibition of the ROS‐p38 MAPK axis increased the survival of VCR‐treated cells and repressed TNF‐α up‐regulation. In contrast to suppression of the ROS‐p38 MAPK axis, overexpression of SIRT3 modestly inhibited the effect of VCR on microtubule destabilization and mitotic arrest in U937 cells. Apoptosis of HL‐60 cells, similarly, went through the same pathway. Collectively, our data indicate that the SIRT3‐ROS‐p38 MAPK‐PP2A‐TTP axis modulates TNF‐α expression, which triggers apoptosis of VCR‐treated U937 and HL‐60 cells. We also demonstrate that the apoptotic signalling is not affected by VCR‐elicited microtubule destabilization.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
</listBibl>
</div1>
</back>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000057 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 000057 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= ChloroquineV1 |flux= Main |étape= Merge |type= RBID |clé= PMC:7028858 |texte= SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:31930676" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \ | NlmPubMed2Wicri -a ChloroquineV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |