Neurotrophin dependence domain -: A domain required for the mediation of apoptosis by the p75 neurotrophin receptor

被引：31

作者：

Rabizadeh, S

Ye, X

Sperandio, S

Wang, JJL

Ellerby, HM

Ellerby, LM

Giza, C

Andrusiak, RL

Frankowski, H

Yaron, Y

Moayeri, NN

Rovelli, G

Evans, CJ

Butcher, LL

Nolan, GP

Assa-Munt, N

Bredesen, DE

机构：

[1] Buck Inst Age Res, Novato, CA 94945 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Burnham Inst, Program Aging, La Jolla, CA 92037 USA

[4] Burnham Inst, Program Struct Biol, La Jolla, CA 92037 USA

[5] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA

[6] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA

[7] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA

[8] Univ Calif Los Angeles, Med Sci Training Program, Los Angeles, CA 90024 USA

[9] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA

[10] Novartis Pharmaceut AG, Basel, Switzerland

[11] Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA

[12] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA

来源：

JOURNAL OF MOLECULAR NEUROSCIENCE | 2000年 / 15卷 / 03期

关键词：

p75(NTR); apoptosis; dependence; neurotrophin; dimerization;

D O I：

10.1385/JMN:15:3:215

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The mechanisms underlying neurotrophin dependence, and cellular dependent states in general, are unknown. We show that a 29 amino acid region in the intracellular domain of the common neurotrophin receptor, p75(NTR), is required for the mediation of apoptosis by p75(NTR) Furthermore, contrary to results obtained with Fas, monomeric p75(NTR) is required for apoptosis induction, whereas multimerization inhibits the pro-apoptotic effect. Within the 29-residue domain required for apoptosis induction by p75(NTR), a 14-residue region is sufficient as a peptide inducer of apoptosis. This 14-residue peptide requires the positively charged carboxyterminal residues for its effect on cell death, and these same residues are required by the full-length p75(NTR). These studies define a novel type of domain that mediates neurotrophin dependence, and suggest that other cellular dependent states may be mediated by proteins displaying similar domains.

引用

页码：215 / 229

页数：15

共 49 条

[31] IS P75(NGFR) INVOLVED IN DEVELOPMENTAL NEURAL CELL-DEATH [J].