DeltaFosB, but not FosB, induces delayed apoptosis independent of cell proliferation in the Rat1a embryo cell line.
The fates of Rat1a cells expressing FosB and DeltaFosB as fusion proteins (ER-FosB, ER-DeltaFosB) with the ligand binding domain of human estrogen receptor were examined. The binding of estrogen to the fusion proteins resulted in their nuclear translocation and triggered cell proliferation, and thereafter delayed cell death was observed only in cells expressing ER-DeltaFosB. The proliferation of Rat1a cells, but not cell death triggered by ER-DeltaFosB, was completely abolished by butyrolactone I, an inhibitor of cycline-dependent kinases, and was partly suppressed by antisense oligonucleotides against galectin-1, whose expression is induced after estrogen administration. The cell death was accompanied by the activation of caspase-3 and -9, the fragmentation of the nuclear genome and cytochrome c release from the mitochondria, and was suppressed by zDEVD-fmk and zLEHD-fmk but not zIETD-fmk. The cell death was not suppressed by exogenous His-PTD-Bcl-x(L) at all, suggesting involvement of a Bcl-x(L)-resistant pathway for cytochrome c release.
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Maidashi Higashi-ku, Fukuoka, Japan.
K
K
Tahara
D
D
Tsuchimoto
Y
Y
Tominaga
S
S
Asoh
S
S
Ohta
M
M
Kitagawa
H
H
Horie
T
T
Kadoya
Y
Y
Nakabeppu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D004967:Estrogens / Q000494:pharmacology; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008854:Microscopy, Electron; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D004967:Estrogens; D037483:Galectin 1; D020033:Protein Isoforms; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D045304:Cytochromes c; D020169:Caspases