PMID- 18469528
OWN - NLM
STAT- MEDLINE
DCOM- 20080929
LR  - 20220309
IS  - 1551-4005 (Electronic)
IS  - 1551-4005 (Linking)
VI  - 7
IP  - 11
DP  - 2008 Jun 1
TI  - (Un)expected roles of c-IAPs in apoptotic and NFkappaB signaling pathways.
PG  - 1511-21
AB  - A family of anti-apoptotic regulators known as inhibitor of apoptosis (IAP) 
      proteins block cell death in response to diverse stimuli. In spite of the fact 
      that cellular IAP1 and 2 (c-IAP1 and 2) were discovered more than 12 years ago, 
      their physiological roles have remained obscure. Several molecular mechanisms 
      were proposed to explain their anti-apoptotic activity, ranging from direct 
      inhibition and ubiquitination of pro-apoptotic molecules, to the activation of 
      pro-survival signaling. New findings present a surprising and complex twists. On 
      the one hand, cIAP1 and c-IAP2 suppress Tumor Necrosis Factor alpha (TNFalpha) 
      stimulated cell death by preventing formation of the TNF Receptor 1 (TNFR1) 
      pro-apoptotic signaling complex. On the other hand, they regulate pro-survival 
      NFkappaB signaling pathways: in the non-canonical pathway, by ubiquitination of 
      NFkappaB-inducing kinase (NIK), and in the canonical pathway, by a 
      yet-to-be-defined mechanism. In addition, c-IAPs self-regulate their protein 
      levels through RING domain mediated auto-ubiquitination. Here, we discuss the 
      most recent progress in our understanding of the biological roles of c-IAPs, as 
      well as the implications of targeting c-IAPs for therapeutic intervention.
FAU - Varfolomeev, Eugene
AU  - Varfolomeev E
AD  - Department of Protein Engineering, Genentech, Inc. South San Francisco, 
      California 94080, USA.
FAU - Vucic, Domagoj
AU  - Vucic D
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20080316
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Apoptosis/genetics/*physiology
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins/genetics/*metabolism
MH  - *Models, Molecular
MH  - NF-kappa B/*metabolism
MH  - Signal Transduction/*genetics
MH  - Tumor Necrosis Factor-alpha/metabolism
RF  - 157
EDAT- 2008/05/13 09:00
MHDA- 2008/09/30 09:00
CRDT- 2008/05/13 09:00
PHST- 2008/05/13 09:00 [pubmed]
PHST- 2008/09/30 09:00 [medline]
PHST- 2008/05/13 09:00 [entrez]
AID - 5959 [pii]
AID - 10.4161/cc.7.11.5959 [doi]
PST - ppublish
SO  - Cell Cycle. 2008 Jun 1;7(11):1511-21. doi: 10.4161/cc.7.11.5959. Epub 2008 Mar 
      16.