Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons

被引:250
作者
Sadoul, R
Fernandez, PA
Quiquerez, AL
Martinou, I
Maki, M
Schroter, M
Becherer, JD
Irmler, M
Tschopp, J
Martinou, JC
机构
[1] GENEVA BIOMED RES INST, CH-1228 PLAN LES OUATES, GENEVA, SWITZERLAND
[2] KYOTO UNIV, INST VIRUS RES, KYOTO, JAPAN
[3] UNIV LAUSANNE, INST BIOCHIM, CH-1066 EPALINGES, SWITZERLAND
[4] GLAXO INC, RES TRIANGLE PK, NC 27709 USA
关键词
interleukin-1 beta converting enzyme; nerve growth factor; programmed cell death; proteasome; sympathetic neurons;
D O I
10.1002/j.1460-2075.1996.tb00758.x
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
Sympathetic neurons undergo programmed cell death (PCD) upon deprivation of nerve growth factor (NGF). PCD of neurons is blocked by inhibitors of the interleukin-1 beta converting enzyme (ICE)/Ced3-like cysteine protease, indicating involvement of this class of proteases in the cell death programme. Here we demonstrate that the proteolytic activities of the proteasome are also essential in PCD of neurons. Nanomolar concentrations of several proteasome inhibitors, including the highly selective inhibitor lactacystin, not only prolonged survival of NGF-deprived neurons but also prevented processing of poly(ADP-ribose) polymerase which is known to be cleaved by an ICE/Ced-3 family member during PCD. These results demonstrate that the proteasome is a key regulator of neuronal PCD and that, within this process, it is involved upstream of proteases of the ICE/Ced-3 family. This order of events was confirmed in macrophages where lactacystin inhibited the proteolytic activation of precursor ICE and the subsequent generation of active interleukin-1 beta.
引用
收藏
页码:3845 / 3852
页数:8
相关论文
共 58 条
[1]   STIMULATION-DEPENDENT I-KAPPA-B-ALPHA PHOSPHORYLATION MARKS THE NF-KAPPA-B INHIBITOR FOR DEGRADATION VIA THE UBIQUITIN-PROTEASOME PATHWAY [J].
ALKALAY, I ;
YARON, A ;
HATZUBAI, A ;
ORIAN, A ;
CIECHANOVER, A ;
BEN-NERIAH, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (23) :10599-10603
[2]   MAMMALIAN SUBTILISINS - THE LONG-SOUGHT DIBASIC PROCESSING ENDOPROTEASES [J].
BARR, PJ .
CELL, 1991, 66 (01) :1-3
[3]  
BARRETT AJ, 1981, METHOD ENZYMOL, V80, P771
[4]   INHIBITION OF ICE FAMILY PROTEASES BY BACULOVIRUS ANTIAPOPTOTIC PROTEIN P35 [J].
BUMP, NJ ;
HACKETT, M ;
HUGUNIN, M ;
SESHAGIRI, S ;
BRADY, K ;
CHEN, P ;
FERENZ, C ;
FRANKLIN, S ;
GHAYUR, T ;
LI, P ;
LICARI, P ;
MANKOVICH, J ;
SHI, LF ;
GREENBERG, AH ;
MILLER, LK ;
WONG, WW .
SCIENCE, 1995, 269 (5232) :1885-1888
[6]   POLY(ADP-RIBOSE) POLYMERASE - A MOLECULAR NICK-SENSOR [J].
DEMURCIA, G ;
DEMURCIA, JM .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (04) :172-176
[7]   MECHANISMS AND FUNCTIONS OF CELL-DEATH [J].
ELLIS, RE ;
YUAN, JY ;
HORVITZ, HR .
ANNUAL REVIEW OF CELL BIOLOGY, 1991, 7 :663-698
[8]   INHIBITION OF PROTEASOME ACTIVITIES AND SUBUNIT-SPECIFIC AMINO-TERMINAL THREONINE MODIFICATION BY LACTACYSTIN [J].
FENTEANY, G ;
STANDAERT, RF ;
LANE, WS ;
CHOI, S ;
COREY, EJ ;
SCHREIBER, SL .
SCIENCE, 1995, 268 (5211) :726-731
[9]  
FIGUEIREDOPEREIRA ME, 1994, J NEUROCHEM, V63, P1578
[10]   PREVENTION OF VERTEBRATE NEURONAL DEATH BY THE CRMA GENE [J].
GAGLIARDINI, V ;
FERNANDEZ, PA ;
LEE, RKK ;
DREXLER, HCA ;
ROTELLO, RJ ;
FISHMAN, MC ;
YUAN, J .
SCIENCE, 1994, 263 (5148) :826-828