schliessen

Filtern

 

Bibliotheken

Induction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species.

Cell cycle progression requires a series of highly coordinated events that ultimately lead to faithful segregation of chromosomes. Aurora B is an essential mitotic kinase, which is involved in regulation of microtubule-kinetochore attachments and cytokinesis. Inhibition of Aurora B results in stabil... Full description

Journal Title: The Journal of biological chemistry June 6, 2014, Vol.289(23), pp.16072-16084
Main Author: Kumari, Geeta
Other Authors: Ulrich, Tanja , Krause, Michael , Finkernagel, Florian , Gaubatz, Stefan
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1083-351X ; DOI: 10.1074/jbc.M114.555060
Link: http://search.proquest.com/docview/1549630935/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1549630935
title: Induction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species.
format: Article
creator:
  • Kumari, Geeta
  • Ulrich, Tanja
  • Krause, Michael
  • Finkernagel, Florian
  • Gaubatz, Stefan
subjects:
  • Aneuploidy–Drug Effects
  • Aurora Kinase B–Biosynthesis
  • Cell Cycle–Pharmacology
  • Cell Line–Metabolism
  • Cyclin-Dependent Kinase Inhibitor P21–Metabolism
  • Flow Cytometry–Metabolism
  • Humans–Metabolism
  • In Situ Hybridization, Fluorescence–Metabolism
  • Protein Kinase Inhibitors–Metabolism
  • Reactive Oxygen Species–Metabolism
  • Signal Transduction–Metabolism
  • P38 Mitogen-Activated Protein Kinases–Metabolism
  • Cyclin-Dependent Kinase Inhibitor P21
  • Protein Kinase Inhibitors
  • Reactive Oxygen Species
  • Aurora Kinase B
  • P38 Mitogen-Activated Protein Kinases
  • Aneuploidy
  • Aurora B
  • Cell Cycle
ispartof: The Journal of biological chemistry, June 6, 2014, Vol.289(23), pp.16072-16084
description: Cell cycle progression requires a series of highly coordinated events that ultimately lead to faithful segregation of chromosomes. Aurora B is an essential mitotic kinase, which is involved in regulation of microtubule-kinetochore attachments and cytokinesis. Inhibition of Aurora B results in stabilization of p53 and induction of p53-target genes such as p21 to inhibit proliferation. We have previously demonstrated that induction of p21 by p53 after inhibition of Aurora B is dependent on the p38 MAPK, which promotes transcriptional elongation of p21 by RNA Pol II. In this study, we show that a subset of p53-target genes are induced in a p38-dependent manner upon inhibition of Aurora B. We also demonstrate that inhibition of Aurora B results in down-regulation of E2F-mediated transcription and that the cell cycle arrest after Aurora B inhibition depends on p53 and pRB tumor suppressor pathways. In addition, we report that activation of p21 after inhibition of Aurora B is correlated with increased chromosome missegregation and aneuploidy but not with binucleation or tetraploidy. We provide evidence that p21 is activated in aneuploid cells by reactive oxygen species (ROS) and p38 MAPK. Finally, we demonstrate that certain drugs that act on aneuploid cells synergize with inhibitors of Aurora B to inhibit colony formation and oncogenic transformation. These findings provide an important link between aneuploidy and the stress pathways activated by Aurora B inhibition and also support the use of Aurora B inhibitors in combination therapy for treatment of cancer.
language: eng
source:
identifier: E-ISSN: 1083-351X ; DOI: 10.1074/jbc.M114.555060
fulltext: fulltext
issn:
  • 1083351X
  • 1083-351X
url: Link


@attributes
ID1848957072
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1549630935
sourceidproquest
recordidTN_proquest1549630935
sourcesystemPC
pqid1549630935
display
typearticle
titleInduction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species.
creatorKumari, Geeta ; Ulrich, Tanja ; Krause, Michael ; Finkernagel, Florian ; Gaubatz, Stefan
contributorKumari, Geeta (correspondence author) ; Kumari, Geeta (record owner)
ispartofThe Journal of biological chemistry, June 6, 2014, Vol.289(23), pp.16072-16084
identifierE-ISSN: 1083-351X ; DOI: 10.1074/jbc.M114.555060
subjectAneuploidy–Drug Effects ; Aurora Kinase B–Biosynthesis ; Cell Cycle–Pharmacology ; Cell Line–Metabolism ; Cyclin-Dependent Kinase Inhibitor P21–Metabolism ; Flow Cytometry–Metabolism ; Humans–Metabolism ; In Situ Hybridization, Fluorescence–Metabolism ; Protein Kinase Inhibitors–Metabolism ; Reactive Oxygen Species–Metabolism ; Signal Transduction–Metabolism ; P38 Mitogen-Activated Protein Kinases–Metabolism ; Cyclin-Dependent Kinase Inhibitor P21 ; Protein Kinase Inhibitors ; Reactive Oxygen Species ; Aurora Kinase B ; P38 Mitogen-Activated Protein Kinases ; Aneuploidy ; Aurora B ; Cell Cycle
languageeng
source
descriptionCell cycle progression requires a series of highly coordinated events that ultimately lead to faithful segregation of chromosomes. Aurora B is an essential mitotic kinase, which is involved in regulation of microtubule-kinetochore attachments and cytokinesis. Inhibition of Aurora B results in stabilization of p53 and induction of p53-target genes such as p21 to inhibit proliferation. We have previously demonstrated that induction of p21 by p53 after inhibition of Aurora B is dependent on the p38 MAPK, which promotes transcriptional elongation of p21 by RNA Pol II. In this study, we show that a subset of p53-target genes are induced in a p38-dependent manner upon inhibition of Aurora B. We also demonstrate that inhibition of Aurora B results in down-regulation of E2F-mediated transcription and that the cell cycle arrest after Aurora B inhibition depends on p53 and pRB tumor suppressor pathways. In addition, we report that activation of p21 after inhibition of Aurora B is correlated with increased chromosome missegregation and aneuploidy but not with binucleation or tetraploidy. We provide evidence that p21 is activated in aneuploid cells by reactive oxygen species (ROS) and p38 MAPK. Finally, we demonstrate that certain drugs that act on aneuploid cells synergize with inhibitors of Aurora B to inhibit colony formation and oncogenic transformation. These findings provide an important link between aneuploidy and the stress pathways activated by Aurora B inhibition and also support the use of Aurora B inhibitors in combination therapy for treatment of cancer.
version3
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1549630935/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Kumari, Geeta
1Ulrich, Tanja
2Krause, Michael
3Finkernagel, Florian
4Gaubatz, Stefan
titleInduction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species.
subject
0Aneuploidy–Drug Effects
1Aurora Kinase B–Biosynthesis
2Cell Cycle–Pharmacology
3Cell Line–Metabolism
4Cyclin-Dependent Kinase Inhibitor P21–Metabolism
5Flow Cytometry–Metabolism
6Humans–Metabolism
7In Situ Hybridization, Fluorescence–Metabolism
8Protein Kinase Inhibitors–Metabolism
9Reactive...
10Aneuploidy
11Aurora B
12Cell Cycle
13Reactive Oxygen Species (ROS)
14Retinoblastoma Protein (pRb, RB)
15p21
16p38 MAPK
17p53
general
0English
110.1074/jbc.M114.555060
2MEDLINE (ProQuest)
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Biological Science Database
7Natural Science Collection
8SciTech Premium Collection
9Health Research Premium Collection
10Health Research Premium Collection (Alumni edition)
11Biological Science Index (ProQuest)
sourceidproquest
recordidproquest1549630935
issn
01083351X
11083-351X
rsrctypearticle
creationdate2014
addtitleThe Journal of biological chemistry
searchscope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
scope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
lsr43
01007527false
11007944false
21009130false
310000004false
410000038false
510000050false
610000120false
710000159false
810000238false
910000253false
1010000260false
1110000270false
1210000271false
1310000302false
1410000350false
contributorKumari, Geeta
startdate20140606
enddate20140606
citationpf 16072 pt 16084 vol 289 issue 23
lsr30VSR-Enriched:[description, pqid]
sort
titleInduction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species.
authorKumari, Geeta ; Ulrich, Tanja ; Krause, Michael ; Finkernagel, Florian ; Gaubatz, Stefan
creationdate20140606
lso0120140606
facets
frbrgroupid7130416252344003304
frbrtype5
newrecords20181218
languageeng
creationdate2014
topic
0Aneuploidy–Drug Effects
1Aurora Kinase B–Biosynthesis
2Cell Cycle–Pharmacology
3Cell Line–Metabolism
4Cyclin-Dependent Kinase Inhibitor P21–Metabolism
5Flow Cytometry–Metabolism
6Humans–Metabolism
7In Situ Hybridization, Fluorescence–Metabolism
8Protein Kinase Inhibitors–Metabolism
9Reactive...
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
9Biological Science Index (ProQuest)
prefilterarticles
rsrctypearticles
creatorcontrib
0Kumari, Geeta
1Ulrich, Tanja
2Krause, Michael
3Finkernagel, Florian
4Gaubatz, Stefan
jtitleJournal of biological chemistry
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Kumari
1Ulrich
2Krause
3Finkernagel
4Gaubatz
aufirst
0Geeta
1Tanja
2Michael
3Florian
4Stefan
au
0Kumari, Geeta
1Ulrich, Tanja
2Krause, Michael
3Finkernagel, Florian
4Gaubatz, Stefan
addauKumari, Geeta
atitleInduction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species.
jtitleThe Journal of biological chemistry
risdate20140606
volume289
issue23
spage16072
epage16084
pages16072-16084
eissn1083-351X
formatjournal
genrearticle
ristypeJOUR
doi10.1074/jbc.M114.555060
urlhttp://search.proquest.com/docview/1549630935/
date2014-06-06