Dimerization-dependent block of the proapoptotic effect of p75(NTR).
The biochemical mechanism by which neurons become dependent on neurotrophins for survival is unknown. We found previously that the common neurotrophin receptor, p75(NTR), is a mediator of neurotrophin dependence and that this effect requires a novel type of domain dubbed a neurotrophin dependence domain. We report here that, in contrast to other proapoptotic receptors such as Fas, apoptosis induction by p75(NTR) requires monomerization, with dimerization inhibiting the effect. Blocking the proapoptotic effect of the monomer by dimerization requires a distinct domain that lies at the carboxyterminus of p75(NTR). These results define a novel type of domain required for inhibiting apoptosis induction by p75(NTR).
Wang
J J
JJ
Program on Aging, The Burnham Institute, La Jolla, CA, USA.
Rabizadeh
S
S
Tasinato
A
A
Sperandio
S
S
Ye
X
X
Green
M
M
Assa-Munt
N
N
Spencer
D
D
Bredesen
D E
DE
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019281:Dimerization; D006801:Humans; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D014162:Transfection
C119717:AP 1510; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D016559:Tacrolimus