An alternatively spliced C-elegans ced-4 RNA encodes a novel cell death inhibitor

被引:125
作者
Shaham, S [1 ]
Horvitz, HR [1 ]
机构
[1] MIT,DEPT BIOL,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139
关键词
D O I
10.1016/S0092-8674(00)80092-6
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 C. elegans gene ced-4 is essential for programmed cell death. We report that ced-4 encodes two transcripts and that whereas the major transcript can cause programmed cell death, the minor transcript can act oppositely and prevent programmed cell death, thus defining a novel class of cell death inhibitors. That ced-4 has both cell-killing and cell-protective functions is consistent with previous genetic studies. Our results suggest that the dual protective and killer functions of the C. elegans bcl-2-like gene ced-9 are mediated by inhibition of the killer and protective ced-4 functions, respectively. We propose that a balance between opposing ced-4 functions influences the decision of a cell to live or to die by programmed cell death and that both ced-9 and ced-4 protective functions are required to prevent programmed cell death.
引用
收藏
页码:201 / 208
页数:8
相关论文
共 44 条
[1]   BCL-X, A BCL-2-RELATED GENE THAT FUNCTIONS AS A DOMINANT REGULATOR OF APOPTOTIC CELL-DEATH [J].
BOISE, LH ;
GONZALEZGARCIA, M ;
POSTEMA, CE ;
DING, LY ;
LINDSTEN, T ;
TURKA, LA ;
MAO, XH ;
NUNEZ, G ;
THOMPSON, CB .
CELL, 1993, 74 (04) :597-608
[2]  
BRENNER S, 1974, GENETICS, V77, P71
[3]   INDUCTION OF APOPTOSIS BY THE BCL-2 HOMOLOG BAK [J].
CHITTENDEN, T ;
HARRINGTON, EA ;
OCONNOR, R ;
FLEMINGTON, C ;
LUTZ, RJ ;
EVAN, GI ;
GUILD, BC .
NATURE, 1995, 374 (6524) :733-736
[4]  
Cortazzo M, 1996, CANCER RES, V56, P1199
[5]   DEATH AND THE CELL [J].
DUVALL, E ;
WYLLIE, AH .
IMMUNOLOGY TODAY, 1986, 7 (04) :115-119
[6]   GENETIC-CONTROL OF PROGRAMMED CELL-DEATH IN THE NEMATODE C-ELEGANS [J].
ELLIS, HM ;
HORVITZ, HR .
CELL, 1986, 44 (06) :817-829
[7]   MECHANISMS AND FUNCTIONS OF CELL-DEATH [J].
ELLIS, RE ;
YUAN, JY ;
HORVITZ, HR .
ANNUAL REVIEW OF CELL BIOLOGY, 1991, 7 :663-698
[8]  
EMMONS SW, 1988, NEMATODE CAENORHABDI, P47
[9]   CLONING OF A BCL-2 HOMOLOG BY INTERACTION WITH ADENOVIRUS E1B 19K [J].
FARROW, SN ;
WHITE, JHM ;
MARTINOU, I ;
RAVEN, T ;
PUN, KT ;
GRINHAM, CJ ;
MARTINOU, JC ;
BROWN, R .
NATURE, 1995, 374 (6524) :731-733
[10]   A NOVEL HUMAN PROTEASE SIMILAR TO THE INTERLEUKIN-1-BETA CONVERTING-ENZYME INDUCES APOPTOSIS IN TRANSFECTED CELLS [J].
FAUCHEU, C ;
DIU, A ;
CHAN, AWE ;
BLANCHET, AM ;
MIOSSEC, C ;
HERVE, F ;
COLLARDDUTILLEUL, V ;
GU, Y ;
ALDAPE, RA ;
LIPPKE, JA ;
ROCHER, C ;
SU, MSS ;
LIVINGSTON, DJ ;
HERCEND, T ;
LALANNE, JL .
EMBO JOURNAL, 1995, 14 (09) :1914-1922