PMID- 15485892
OWN - NLM
STAT- MEDLINE
DCOM- 20050721
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 1
DP  - 2005 Jan 7
TI  - Identification of a network involved in thapsigargin-induced apoptosis using a 
      library of small interfering RNA expression vectors.
PG  - 826-31
AB  - We describe here the construction of a library of small interfering RNA 
      expression vectors targeted to a few hundred apoptosis-related genes and the 
      application of this library to an investigation of thapsigargin (TG)-induced 
      apoptosis. Thapsigargin triggers endoplasmic reticulum stress, with subsequent 
      apoptosis, but the molecular mechanisms underlying this process are incompletely 
      understood. Using our library, we identified three anti-apoptotic genes, namely, 
      NOXA, E2F1, and MAPK1, in addition to already characterized genes in the 
      apoptotic pathway. In contrast to proposals by others, our data revealed (i) that 
      TG-induced apoptosis is associated with Apaf1 in a caspase-3- and 
      caspase-9-independent manner; (ii) that the E2F1-PUMA pathway might be involved; 
      and (iii) that the ERK pathway, via MAP3K8 (mitogen-activated protein kinase 
      kinase 8), is required for the induction by TG of apoptosis. Our study 
      demonstrates clearly that unexpected and novel genes can be identified 
      effectively by our method, and it provides evidence for the efficacy and utility 
      of the comprehensive analysis of signaling networks and pathways using a library 
      of small interfering RNA expression vectors.
FAU - Futami, Takashi
AU  - Futami T
AD  - Department of Chemistry and Biotechnology, School of Engineering, The University 
      of Tokyo, Hongo, Tokyo 113-8656, Japan.
FAU - Miyagishi, Makoto
AU  - Miyagishi M
FAU - Taira, Kazunari
AU  - Taira K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041014
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (RNA, Small Interfering)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*genetics
MH  - Gene Library
MH  - Humans
MH  - RNA, Small Interfering/*genetics
MH  - Signal Transduction/*genetics
MH  - Thapsigargin/pharmacology
EDAT- 2004/10/16 09:00
MHDA- 2005/07/22 09:00
CRDT- 2004/10/16 09:00
PHST- 2004/10/16 09:00 [pubmed]
PHST- 2005/07/22 09:00 [medline]
PHST- 2004/10/16 09:00 [entrez]
AID - S0021-9258(20)76651-2 [pii]
AID - 10.1074/jbc.M409948200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Jan 7;280(1):826-31. doi: 10.1074/jbc.M409948200. Epub 2004 Oct 
      14.