Role of c-myc in simian virus 40 large tumor antigen-induced DNA synthesis in quiescent 3T3-L1 mouse fibroblasts.
Stably transfected NIH 3T3-L1 mouse fibroblasts (L1 cells) expressing the simian virus 40 large tumor antigen (LTAg) maintain c-myc expression and proliferation in low serum, whereas cells expressing the mutant form LTAg-K1, defective in binding of the retinoblastoma suppressor gene product pRb, showed reduced levels of c-myc RNA and only background levels of DNA synthesis in low serum. The role of the c-Myc protein in LTAg-induced DNA synthesis was studied in microinjection experiments. Expression of LTAg induced cellular DNA synthesis in > 95% of microinjected serum-starved L1 cells, whereas the mutant LTAg-K1 could not induce DNA synthesis. Coexpression of dominant negative c-Myc or Max mutants with LTAg inhibited DNA synthesis, indicating that functional c-Myc is necessary for induction of DNA synthesis by LTAg. Expression of c-Myc induced programmed cell death (apoptosis) in serum-starved L1 cells. Coexpression of c-Myc with LTAg-K1 restored induction of DNA synthesis without apoptosis. Expression of a truncated LTAg, LTAg-(1-259), defective in binding of the tumor suppressor gene product p53, failed to prevent c-Myc-induced apoptosis. The data indicate that c-Myc can restore the ability of LTAg-K1 to induce DNA synthesis and that LTAg-K1 prevents c-Myc-induced apoptosis in serum-starved L1 cells by its interaction with p53.
Hermeking
H
H
Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit, Munich, Germany.
Wolf
D A
DA
Kohlhuber
F
F
Dickmanns
A
A
Billaud
M
M
Fanning
E
E
Eick
D
D
D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression; D016259:Genes, myc; D007700:Kinetics; D051379:Mice; D010957:Plasmids; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C068422:Max protein, mouse; D004247:DNA