PMID- 18606850
OWN - NLM
STAT- MEDLINE
DCOM- 20080808
LR  - 20211020
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 182
IP  - 1
DP  - 2008 Jul 14
TI  - TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to 
      sensitize tumor cells to TNFalpha.
PG  - 171-84
LID - 10.1083/jcb.200801010 [doi]
AB  - Synthetic inhibitor of apoptosis (IAP) antagonists induce degradation of IAP 
      proteins such as cellular IAP1 (cIAP1), activate nuclear factor kappaB 
      (NF-kappaB) signaling, and sensitize cells to tumor necrosis factor alpha 
      (TNFalpha). The physiological relevance of these discoveries to cIAP1 function 
      remains undetermined. We show that upon ligand binding, the TNF superfamily 
      receptor FN14 recruits a cIAP1-Tnf receptor-associated factor 2 (TRAF2) complex. 
      Unlike IAP antagonists that cause rapid proteasomal degradation of cIAP1, 
      signaling by FN14 promotes the lysosomal degradation of cIAP1-TRAF2 in a 
      cIAP1-dependent manner. TNF-like weak inducer of apoptosis (TWEAK)/FN14 signaling 
      nevertheless promotes the same noncanonical NF-kappaB signaling elicited by IAP 
      antagonists and, in sensitive cells, the same autocrine TNFalpha-induced death 
      occurs. TWEAK-induced loss of the cIAP1-TRAF2 complex sensitizes immortalized and 
      minimally passaged tumor cells to TNFalpha-induced death, whereas primary cells 
      remain resistant. Conversely, cIAP1-TRAF2 complex overexpression limits FN14 
      signaling and protects tumor cells from TWEAK-induced TNFalpha sensitization. 
      Lysosomal degradation of cIAP1-TRAF2 by TWEAK/FN14 therefore critically alters 
      the balance of life/death signals emanating from TNF-R1 in immortalized cells.
FAU - Vince, James E
AU  - Vince JE
AD  - Department of Biochemistry, La Trobe University, Kingsbury Drive, Melbourne, VIC 
      3086, Australia.
FAU - Chau, Diep
AU  - Chau D
FAU - Callus, Bernard
AU  - Callus B
FAU - Wong, W Wei-Lynn
AU  - Wong WW
FAU - Hawkins, Christine J
AU  - Hawkins CJ
FAU - Schneider, Pascal
AU  - Schneider P
FAU - McKinlay, Mark
AU  - McKinlay M
FAU - Benetatos, Christopher A
AU  - Benetatos CA
FAU - Condon, Stephen M
AU  - Condon SM
FAU - Chunduru, Srinivas K
AU  - Chunduru SK
FAU - Yeoh, George
AU  - Yeoh G
FAU - Brink, Robert
AU  - Brink R
FAU - Vaux, David L
AU  - Vaux DL
FAU - Silke, John
AU  - Silke J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080707
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (TNFRSF12A protein, human)
RN  - 0 (TWEAK Receptor)
RN  - 0 (Tnfrsf12a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.- (Cathepsins)
SB  - IM
CIN - J Cell Biol. 2008 Jul 14;182(1):15-7. PMID: 18606854
MH  - Animals
MH  - Caspase Inhibitors
MH  - Cathepsins/metabolism
MH  - Cell Death/drug effects
MH  - Cell Line, Transformed
MH  - Cell Line, Tumor
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins/chemistry/*metabolism
MH  - Lysosomes/drug effects/*metabolism
MH  - Mice
MH  - Models, Biological
MH  - NF-kappa B/metabolism
MH  - Protein Binding/drug effects
MH  - Protein Processing, Post-Translational/*drug effects
MH  - Protein Structure, Tertiary
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Signal Transduction/*drug effects
MH  - TNF Receptor-Associated Factor 2/*metabolism
MH  - TWEAK Receptor
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC2447903
EDAT- 2008/07/09 09:00
MHDA- 2008/08/09 09:00
PMCR- 2009/01/14
CRDT- 2008/07/09 09:00
PHST- 2008/07/09 09:00 [pubmed]
PHST- 2008/08/09 09:00 [medline]
PHST- 2008/07/09 09:00 [entrez]
PHST- 2009/01/14 00:00 [pmc-release]
AID - jcb.200801010 [pii]
AID - 200801010 [pii]
AID - 10.1083/jcb.200801010 [doi]
PST - ppublish
SO  - J Cell Biol. 2008 Jul 14;182(1):171-84. doi: 10.1083/jcb.200801010. Epub 2008 Jul 
      7.