Myc drives apoptosis in PC12 cells in the absence of Max.
A conditionally active chimeric form of the c-Myc protein fused to the ligand-binding domain of the estrogen receptor (MycER) was expressed in PC12 cells. Induction of Myc activity resulted in a threefold increase in apoptosis after 5 days when cells were maintained in 1% serum. The effect of Myc overexpression was dependent on its DNA-binding domain but not on its heterodimeric binding protein Max, which is absent in PC12 cells. Preincubation of the c-Myc overexpressing cells with either NGF or bFGF, but not EGF, prevented the Myc-mediated increase in apoptosis, although the signaling pathways used by NGF and bFGF to block cell death differed. NGF-mediated rescue was mediated by the phosphatidylinositol 3'-OH (P13) kinase/Akt pathway while rescue by bFGF was not affected by P13 kinase inhibitors. These results show that Myc can induce apoptosis in PC12 cells in a Max-independent manner and that alternate signaling pathways exist to mediate cell survival.
Wert
M
M
Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois, IL 60637, USA.
Kennedy
S
S
Palfrey
H C
HC
Hay
N
N
D000818:Animals; D017209:Apoptosis; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D016716:PC12 Cells; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499329:Max protein, rat; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor