Role of c-myc in simian virus 40 large tumor antigen-induced DNA synthesis in quiescent 3T3-L1 mouse fibroblasts.
AUTOR(ES)
Hermeking, H
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=45030Documentos Relacionados
- Analysis of simian virus 40 small t antigen-induced progression of rat F111 cells minimally transformed by large T antigen.
- Simian virus 40 small-t antigen-induced theophylline resistance is not mediated by cyclic AMP.
- Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells.
- c-myc protein can be substituted for SV40 T antigen in SV40 DNA replication.
- Cell density and paradoxical transcriptional properties of c-Myc and Max in cultured mouse fibroblasts.