Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings

被引:24
作者
Chen, CM [1 ]
Sytkowski, AJ [1 ]
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Hematol & Oncol,Lab Cell & Mol Biol, Cambridge, MA 02138 USA
关键词
Raf-1; ALG-2; ASK1; apoptosis; signal transduction;
D O I
10.1016/j.bbrc.2005.05.074
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
Raf-1 plays important roles in cell proliferation, differentiation, and survival. However, the unique and essential function of Raf-1 is anti-apoptotic. The molecules that mediate Raf-1's anti-apoptotic function are not known. In the course of identifying new substrates of Raf-1, we found that the Raf-1 kinase domain interacted with apoptosis-linked gene-2 (ALG-2) in yeast two-hybrid system. Our further studies showed that Raf-1 phosphorylated ALG-2 in an in vitro kinase assay. We also found that apoptosis signal-regulating kinase 1 (ASK1) strongly phosphorylated ALG-2. Importantly, Raf-1 blocks the ASK1-dependent ALG-2 phosphorylation. Since ALG-2 associates with ASK1, and both ASK1 and ALG-2 are involved in apoptosis, our observations indicate that Raf-1 may mediate its anti-apoptotic function by interrupting ASK1-dependent phosphorylation of ALG-2. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:51 / 57
页数:7
相关论文
共 33 条
  • [11] Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis
    Kim, SD
    Moon, CK
    Eun, SY
    Ryu, PD
    Jo, SA
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 328 (01) : 326 - 334
  • [12] Up-regulation of ALG-2 cancer tissue in hepatomas and lung
    la Cour, JM
    Mollerup, J
    Winding, P
    Tarabykina, S
    Sehested, M
    Berchtold, MW
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (01) : 81 - 89
  • [13] Lacana E, 1997, J IMMUNOL, V158, P5129
  • [14] REQUIREMENT FOR RAS IN RAF ACTIVATION IS OVERCOME BY TARGETING RAF TO THE PLASMA-MEMBRANE
    LEEVERS, SJ
    PATERSON, HF
    MARSHALL, CJ
    [J]. NATURE, 1994, 369 (6479) : 411 - 414
  • [15] Raf induces TGFβ production while blocking its apoptotic but not invasive responses:: a mechanism leading to increased malignancy in epithelial cells
    Lehmann, K
    Janda, E
    Pierreux, CE
    Rytömaa, M
    Schulze, A
    McMahon, M
    Hill, CS
    Beug, H
    Downward, J
    [J]. GENES & DEVELOPMENT, 2000, 14 (20) : 2610 - 2622
  • [16] Activation of apoptosis signal-regulating kinase 1 (ASK1) by tumor necrosis factor receptor-associated factor 2 requires prior dissociation of the ASK1 inhibitor thioredoxin
    Liu, H
    Nishitoh, H
    Ichijo, H
    Kyriakis, JM
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (06) : 2198 - 2208
  • [17] Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene
    Mikula, M
    Schreiber, M
    Husak, Z
    Kucerova, L
    Rüth, J
    Wieser, R
    Zatloukal, K
    Beug, H
    Wagner, EF
    Baccarini, M
    [J]. EMBO JOURNAL, 2001, 20 (08) : 1952 - 1962
  • [18] 14-3-3 - MODULATORS OF SIGNALING PROTEINS
    MORRISON, D
    [J]. SCIENCE, 1994, 266 (5182) : 56 - 57
  • [19] MORRISON DK, 1993, J BIOL CHEM, V268, P17309
  • [20] Raf revealed in life-or-death decisions
    Pritchard, C
    McMahon, M
    [J]. NATURE GENETICS, 1997, 16 (03) : 214 - 215