Neuronal differentiation and protection from nitric oxide-induced apoptosis require c-Jun-dependent expression of NCAM140

被引:41
作者
Feng, ZW [1 ]
Li, L [1 ]
Ng, PY [1 ]
Porter, AG [1 ]
机构
[1] Inst Mol & Cell Biol, Singapore 117609, Singapore
关键词
D O I
10.1128/MCB.22.15.5357-5366.2002
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
c-Jun, a crucial component of the dimeric transcription factor activating protein 1 (AP-1), can regulate apoptosis induced by oxidative stress and has been implicated in neuronal differentiation, but the mechanisms are largely unknown. We found that specific inhibition of transcription or stable transfection with cDNA encoding dominant-negative c-Jun sensitized SH-SYSY neuroblastoma cells (TAM-67 cells) to apoptosis induced by the nitric oxide (NO) donor sodium nitroprusside or SIN-1. TAM-67 cells also became refractory to nerve growth factor (NGF)-induced neuronal differentiation. Dominant-negative c-Jun abolished expression of a 140-kDa neural cell adhesion molecule (NCAM140) and dramatically enhanced the expression of NCAM180 in TAM-67 cells. Inhibition of c-Jun in TAM-67 cells also resulted in a corresponding decrease in the amount of NCAM140 mRNA and an increase in the amount of NCAM180 mRNA. Reexpression of NCAM140 in TAM-67 cells restored NGF-induced neuronal differentiation and resistance to NO-induced apoptosis. Our results show that c-jun/AP-1, through up-regulation of NCAM140, plays an important role in both NGF-induced neuronal differentiation and resistance to apoptosis induced by NO in neuroblastoma cells. As NCAM140 and NCAM180 are translated from differentially spliced mRNAs transcribed from the same gene, alternative splicing of NCAM pre-mRNA (and consequently the synthesis of the smaller NCAM140 species) appears to be regulated by c-Jun/AP-1.
引用
收藏
页码:5357 / 5366
页数:10
相关论文
共 63 条
  • [11] N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling
    Cavallaro, U
    Niedermeyer, J
    Fuxa, M
    Christofori, G
    [J]. NATURE CELL BIOLOGY, 2001, 3 (07) : 650 - 657
  • [12] Directing alternative splicing: Cast and scenarios
    Chabot, B
    [J]. TRENDS IN GENETICS, 1996, 12 (11) : 472 - 478
  • [13] CONSERVED REGULATORY ELEMENTS IN THE PROMOTER REGION OF THE N-CAM GENE
    COLWELL, G
    LI, B
    FORREST, D
    BRACKENBURY, R
    [J]. GENOMICS, 1992, 14 (04) : 875 - 882
  • [14] An element in the 5′ common exon of the NCAM alternative splicing unit interacts with SR proteins and modulates 5′ splice site selection
    Côté, J
    Simard, MJ
    Chabot, B
    [J]. NUCLEIC ACIDS RESEARCH, 1999, 27 (12) : 2529 - 2537
  • [15] OXIDATIVE STRESS, GLUTAMATE, AND NEURODEGENERATIVE DISORDERS
    COYLE, JT
    PUTTFARCKEN, P
    [J]. SCIENCE, 1993, 262 (5134) : 689 - 695
  • [16] Crossin KL, 2000, DEV DYNAM, V218, P260, DOI 10.1002/(SICI)1097-0177(200006)218:2<260::AID-DVDY3>3.0.CO
  • [17] 2-9
  • [18] Doherty P, 1992, Curr Opin Neurobiol, V2, P595, DOI 10.1016/0959-4388(92)90024-F
  • [19] ALTERNATIVE SPLICING OF THE CYTOPLASMIC DOMAIN OF NEURAL CELL-ADHESION MOLECULE ALTERS ITS ABILITY TO ACT AS A SUBSTRATE FOR NEURITE OUTGROWTH
    DOHERTY, P
    RIMON, G
    MANN, DA
    WALSH, FS
    [J]. JOURNAL OF NEUROCHEMISTRY, 1992, 58 (06) : 2338 - 2341
  • [20] c-Jun promotes neurite outgrowth and survival in PC12 cells
    Dragunow, M
    Xu, RA
    Walton, M
    Woodgate, AM
    Lawlor, P
    MacGibbon, GA
    Young, D
    Gibbons, H
    Lipski, J
    Muravlev, A
    Pearson, A
    During, M
    [J]. MOLECULAR BRAIN RESEARCH, 2000, 83 (1-2): : 20 - 33