PMID- 18577757
OWN - NLM
STAT- MEDLINE
DCOM- 20080806
LR  - 20220222
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 1
IP  - 25
DP  - 2008 Jun 24
TI  - An alternative mechanism of eukaryotic translation initiation.
PG  - 32
LID - 10.1126/scisignal.125pe32 [doi]
AB  - Cell stress activates signaling pathways, allowing cells to choose between 
      survival and apoptosis. Translation plays a critical role in balancing this 
      choice by allowing for rapid and physiologically responsive changes in de novo 
      gene expression. The steady-state abundance of cellular inhibitor of apoptosis 2 
      (cIAP2) is increased in response to various cell stresses. This modular protein 
      contains baculoviral IAP repeat (BIR) motifs and ubiquitin protein ligase (E3) 
      activity, which allows it to bind directly to caspases and to modulate activation 
      of the transcription factor, nuclear factor kappaB (NF-kappaB). The messenger RNA 
      (mRNA) encoding cIAP2 is a large 5.5-kb transcript, with a highly structured 5' 
      untranslated region (5'UTR) also containing 64 upstream initiation codons ahead 
      of the true start codon. cIAP2 employs an unusual cap-dependent mechanism of 
      ribosome shunting to bypass the majority of the inhibitory elements in the 5'UTR, 
      a mechanism first described for plant pararetroviruses. Furthermore, in mammalian 
      cells, this poorly understood mechanism of translation for cIAP2 is enhanced 
      during mild stress in the absence of pararetrovirus-encoded proteins known to be 
      essential for this process in plant cells. Here, we discuss how cIAP2 might 
      utilize the stress-mediated shunt process in the absence of viral proteins, which 
      suggests a more widespread role for canonical initiation factors, internal 
      ribosome entry sequence-specific trans-acting factors, and mRNA structure in 
      translational control during stress.
FAU - Morley, Simon J
AU  - Morley SJ
AD  - Department of Biochemistry, School of Life Sciences, University of Sussex, 
      Brighton BN1 9QG, UK. s.j.morley@sussex.ac.uk
FAU - Coldwell, Mark J
AU  - Coldwell MJ
LA  - eng
PT  - Journal Article
DEP - 20080624
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Eukaryotic Initiation Factor-2B)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Cell Division
MH  - Cell Physiological Phenomena
MH  - Eukaryotic Initiation Factor-2B/genetics
MH  - Humans
MH  - Models, Genetic
MH  - Peptide Chain Initiation, Translational/*physiology
MH  - Protein Biosynthesis/physiology
MH  - RNA, Messenger/genetics
MH  - Ribosomes/*physiology
MH  - Signal Transduction
MH  - Stress, Mechanical
EDAT- 2008/06/26 09:00
MHDA- 2008/08/07 09:00
CRDT- 2008/06/26 09:00
PHST- 2008/06/26 09:00 [pubmed]
PHST- 2008/08/07 09:00 [medline]
PHST- 2008/06/26 09:00 [entrez]
AID - scisignal.125pe32 [pii]
AID - 10.1126/scisignal.125pe32 [doi]
PST - epublish
SO  - Sci Signal. 2008 Jun 24;1(25):32. doi: 10.1126/scisignal.125pe32.