Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of p21(CDKN1A)

C. Mlynarczyk, R. Fåhraeus,

. 2014 ; 5 (-) : 5067. [pub] 20141008

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc15031802

Endoplasmic reticulum (ER) stress occurs in poorly perfused tissues and activates the p53 isoform p53/47 to promote G2 arrest via 14-3-3σ. This contrasts with the p21(CDKN1A)-dependent G1 arrest caused by p53 following DNA damage. It is not known how cells respond to conditions when both pathways are activated. Here we show that p53/47 prevents p53-induced p21 transcription during ER stress and that both isoforms repress p21 mRNA translation. This prevents p21 from promoting COP1-mediated 14-3-3σ degradation and leads to G2 arrest. DNA damage does not result in p53-dependent induction of p21 during ER stress and instead results in an increase in p53-induced apoptosis. This illustrates how p53 isoforms target an intrinsic balance between the G1 and G2 checkpoints for cell cycle coordination and demonstrates an ER stress-dependent p53 pathway that suppresses p21 and lowers the apoptotic threshold to genotoxic drugs.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc15031802
003      
CZ-PrNML
005      
20151014100829.0
007      
ta
008      
151005s2014 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/ncomms6067 $2 doi
035    __
$a (PubMed)25295585
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Mlynarczyk, Coraline $u Equipe Labellisée Ligue Contre le Cancer, Université Paris 7, INSERM UMR 1162, 27 rue Juliette Dodu, 75010 Paris, France.
245    10
$a Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of p21(CDKN1A) / $c C. Mlynarczyk, R. Fåhraeus,
520    9_
$a Endoplasmic reticulum (ER) stress occurs in poorly perfused tissues and activates the p53 isoform p53/47 to promote G2 arrest via 14-3-3σ. This contrasts with the p21(CDKN1A)-dependent G1 arrest caused by p53 following DNA damage. It is not known how cells respond to conditions when both pathways are activated. Here we show that p53/47 prevents p53-induced p21 transcription during ER stress and that both isoforms repress p21 mRNA translation. This prevents p21 from promoting COP1-mediated 14-3-3σ degradation and leads to G2 arrest. DNA damage does not result in p53-dependent induction of p21 during ER stress and instead results in an increase in p53-induced apoptosis. This illustrates how p53 isoforms target an intrinsic balance between the G1 and G2 checkpoints for cell cycle coordination and demonstrates an ER stress-dependent p53 pathway that suppresses p21 and lowers the apoptotic threshold to genotoxic drugs.
650    _2
$a proteiny 14-3-3 $x metabolismus $7 D048948
650    _2
$a apoptóza $x genetika $7 D017209
650    12
$a kontrolní body buněčného cyklu $7 D059447
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a inhibitor p21 cyklin-dependentní kinasy $x genetika $x metabolismus $7 D050759
650    _2
$a poškození DNA $x genetika $7 D004249
650    12
$a stres endoplazmatického retikula $7 D059865
650    _2
$a exoribonukleasy $x metabolismus $7 D005095
650    _2
$a kontrolní body fáze G2 buněčného cyklu $7 D059565
650    _2
$a HCT116 buňky $7 D045325
650    _2
$a lidé $7 D006801
650    _2
$a MFC-7 buňky $7 D061986
650    _2
$a nádorové biomarkery $x metabolismus $7 D014408
650    _2
$a nádorový supresorový protein p53 $x genetika $x metabolismus $7 D016159
650    _2
$a ubikvitinligasy $x metabolismus $7 D044767
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Fåhraeus, Robin $u 1] Equipe Labellisée Ligue Contre le Cancer, Université Paris 7, INSERM UMR 1162, 27 rue Juliette Dodu, 75010 Paris, France [2] RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic.
773    0_
$w MED00184850 $t Nature communications $x 2041-1723 $g Roč. 5, č. - (2014), s. 5067
856    41
$u https://pubmed.ncbi.nlm.nih.gov/25295585 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20151005 $b ABA008
991    __
$a 20151014101019 $b ABA008
999    __
$a ok $b bmc $g 1092678 $s 914928
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2014 $b 5 $c - $d 5067 $e 20141008 $i 2041-1723 $m Nature communications $n Nat Commun $x MED00184850
LZP    __
$a Pubmed-20151005

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace