PMID- 10514511
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 42
DP  - 1999 Oct 15
TI  - TRAF family proteins interact with the common neurotrophin receptor and modulate 
      apoptosis induction.
PG  - 30202-8
AB  - The common neurotrophin receptor, p75(NTR), has been shown to signal in the
      absence of Trk tyrosine kinase receptors, including induction of neural apoptosis
      and activation of NF-kappaB. However, the mechanisms by which p75(NTR) initiates 
      these intracellular signal transduction pathways are unknown. Here we report
      interactions between p75(NTR) and the six members of TRAF (tumor necrosis factor 
      receptor-associated factors) family proteins. The binding of different TRAF
      proteins to p75(NTR) was mapped to distinct regions in p75(NTR). Furthermore,
      TRAF4 interacted with dimeric p75(NTR), whereas TRAF2 interacted preferentially
      with monomeric p75(NTR). TRAF2-p75(NTR), TRAF4-p75(NTR), and TRAF6-p75(NTR)
      interactions modulated p75(NTR)-induced cell death and NF-kappaB activation with 
      contrasting effects. Coexpression of TRAF2 with p75(NTR) enhanced cell death,
      whereas coexpression of TRAF6 was cytoprotective. Furthermore, overexpression of 
      TRAF4 abrogated the ability of dimerization to prevent the induction of apoptosis
      normally mediated by monomeric p75(NTR). TRAF4 also inhibited the NF-kappaB
      response, whereas TRAF2 and TRAF6 enhanced p75(NTR)-induced NF-kappaB activation.
      These results demonstrate that TRAF family proteins interact with p75(NTR) and
      differentially modulate its NF-kappaB activation and cell death induction.
FAU - Ye, X
AU  - Ye X
AD  - The Burnham Institute, La Jolla, California 92037, USA.
FAU - Mehlen, P
AU  - Mehlen P
FAU - Rabizadeh, S
AU  - Rabizadeh S
FAU - VanArsdale, T
AU  - VanArsdale T
FAU - Zhang, H
AU  - Zhang H
FAU - Shin, H
AU  - Shin H
FAU - Wang, J J
AU  - Wang JJ
FAU - Leo, E
AU  - Leo E
FAU - Zapata, J
AU  - Zapata J
FAU - Hauser, C A
AU  - Hauser CA
FAU - Reed, J C
AU  - Reed JC
FAU - Bredesen, D E
AU  - Bredesen DE
LA  - eng
GR  - CA69381/CA/NCI NIH HHS/United States
GR  - NS33376/NS/NINDS NIH HHS/United States
GR  - NS35155/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Biopolymers)
RN  - 0 (DNA Primers)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - *Apoptosis
MH  - Base Sequence
MH  - Biopolymers
MH  - Cell Line
MH  - DNA Primers
MH  - Humans
MH  - NF-kappa B/metabolism
MH  - Protein Binding
MH  - Receptors, Nerve Growth Factor/*metabolism
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - *Signal Transduction
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - 10.1074/jbc.274.42.30202 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 15;274(42):30202-8. doi: 10.1074/jbc.274.42.30202.