PMID- 22260869
OWN - NLM
STAT- MEDLINE
DCOM- 20120718
LR  - 20121115
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 206
DP  - 2012 Mar 29
TI  - Arsenite-induced apoptosis of human neuroblastoma cells requires p53 but occurs 
      independently of c-Jun.
PG  - 25-38
LID - 10.1016/j.neuroscience.2012.01.001 [doi]
AB  - Arsenite treatment of human SH-SY5Y neuroblastoma cells leads to an upregulation 
      of caspase-3/7 activity and to the fragmentation of chromatin that is accompanied 
      by elevated p53 and c-Jun levels. Expression of a truncated mutant of p53, p53DD, 
      which interfered with the oligomerization of p53, suppressed the arsenite-induced 
      upregulation of caspase-3/7 activity and the fragmentation of chromatin, 
      indicating that p53 is required for arsenite-induced cell death. These data were 
      corroborated by knockdown experiments of p53 following expression of a 
      p53-specific short hairpin RNA. Likewise, expression of either p53DD or knockdown 
      of p53 prevented caspase-3/7 activation and chromatin fragmentation induced by 
      nutlin-3, a compound that prevents the interaction between p53 and the E3 
      ubiquitin ligase MDM2. Transcriptional upregulation of a chromatin-embedded 
      p53-responsive reporter gene in either arsenite or nutlin-3 stimulated 
      neuroblastoma cells revealed that the transcriptional activity of p53 was 
      increased under these conditions. Expression of a c-Jun-specific short hairpin 
      RNA failed to impair arsenite-induced caspase-3/7 activation and fragmentation of 
      chromatin. Likewise, inhibition of c-Jun target gene expression by expression of 
      a dominant-negative mutant of c-Jun did not interfere with arsenite-induced 
      caspase-3/7 activation and chromatin fragmentation. However, this approach 
      successfully reduced caspase-3/7 activity induced as a result of forced 
      expression of a constitutively active mutant of mitogen-activated protein 
      kinase/extracellular signal-regulated kinase kinase kinase (MEKK)-1. Together, 
      these data show that the upregulation of p53 is causally linked with 
      arsenite-induced cell death in neuroblastoma cells, whereas the upregulation of 
      c-Jun is not part of this apoptotic signaling cascade.
CI  - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Keim, A
AU  - Keim A
AD  - Department of Medical Biochemistry and Molecular Biology, University of Saarland 
      Medical Center, D-66421 Homburg, Germany.
FAU - Rossler, O G
AU  - Rossler OG
FAU - Rothhaar, T L
AU  - Rothhaar TL
FAU - Thiel, G
AU  - Thiel G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120108
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Arsenites)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - N5509X556J (arsenite)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Arsenites/*pharmacology
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Neuroblastoma/*metabolism
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Tumor Suppressor Protein p53/*metabolism
EDAT- 2012/01/21 06:00
MHDA- 2012/07/19 06:00
CRDT- 2012/01/21 06:00
PHST- 2011/11/03 00:00 [received]
PHST- 2011/12/21 00:00 [revised]
PHST- 2012/01/02 00:00 [accepted]
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/07/19 06:00 [medline]
AID - S0306-4522(12)00003-6 [pii]
AID - 10.1016/j.neuroscience.2012.01.001 [doi]
PST - ppublish
SO  - Neuroscience. 2012 Mar 29;206:25-38. doi: 10.1016/j.neuroscience.2012.01.001. 
      Epub 2012 Jan 8.