PMID- 19234489
OWN - NLM
STAT- MEDLINE
DCOM- 20090421
LR  - 20171116
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 28
IP  - 13
DP  - 2009 Apr 2
TI  - TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for 
      activation of NF-kappaB.
PG  - 1584-93
LID - 10.1038/onc.2009.17 [doi]
AB  - Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the 
      most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation 
      occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating 
      protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor 
      of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain 
      of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), 
      but its role in NF-kappaB activation is still unclear. Here, we investigated the 
      role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 
      domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 
      domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to 
      activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, 
      suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for 
      NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or 
      downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB 
      activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of 
      the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A 
      c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided 
      evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases 
      in the NF-kappaB activity, increased expression of endogenous NF-kappaB target 
      genes (c-FLIP, TRAF1), and resistance to apoptosis.
FAU - Garrison, J B
AU  - Garrison JB
AD  - Program on Apoptosis and Cell Death Research, Cancer Center, Burnham Institute 
      for Medical Research, La Jolla, CA 92037, USA.
FAU - Samuel, T
AU  - Samuel T
FAU - Reed, J C
AU  - Reed JC
LA  - eng
PT  - Journal Article
DEP - 20090223
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Cytokines)
RN  - 0 (DIABLO protein, human)
RN  - 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (KCNJ6 protein, human)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (MALT1 protein, human)
RN  - EC 3.4.22.- (Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein)
SB  - IM
MH  - Apoptosis Regulatory Proteins/genetics/metabolism
MH  - Caspases/chemistry/genetics/*metabolism
MH  - Cell Death/drug effects/genetics
MH  - Cells, Cultured
MH  - Cytokines/pharmacology
MH  - Cytoprotection/drug effects/genetics
MH  - Drug Resistance, Neoplasm/genetics
MH  - G Protein-Coupled Inwardly-Rectifying Potassium Channels/*chemistry/metabolism
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins/chemistry/genetics/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Jurkat Cells
MH  - Mitochondrial Proteins/metabolism
MH  - Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
MH  - Mutation/physiology
MH  - NF-kappa B/*metabolism
MH  - Neoplasm Proteins/chemistry/genetics/*metabolism
MH  - Oncogene Proteins, Fusion/chemistry/metabolism/physiology
MH  - Protein Binding/physiology
MH  - Protein Interaction Domains and Motifs/genetics
MH  - TNF Receptor-Associated Factor 2/genetics/*metabolism/physiology
EDAT- 2009/02/24 09:00
MHDA- 2009/04/22 09:00
CRDT- 2009/02/24 09:00
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/04/22 09:00 [medline]
AID - onc200917 [pii]
AID - 10.1038/onc.2009.17 [doi]
PST - ppublish
SO  - Oncogene. 2009 Apr 2;28(13):1584-93. doi: 10.1038/onc.2009.17. Epub 2009 Feb 23.