SV40 small T antigen enhances progression to >G2 during lytic infection.
The infection of monkey kidney (CV-1) cells with simian virus 40 (SV40) stimulates the cells into successive rounds of DNA synthesis without an intervening mitosis, leading to the acquisition of a >G2 DNA content. To elucidate the role of small t antigen in cell cycle progression and in viral replication during infection, studies were performed using an SV40 mutant (dl888) that lacks the ability to produce small t. Initially dl888-infected cells move through the first S phase at roughly the same rate as wild-type infected cells. Upon reaching G2, however, the dl888-infected cells progressed to >G2 at a reduced rate relative to wild-type. The slower rate of entry into >G2 of dl888-infected cells is associated with a decrease in total pRb and an increase in the ratio of hypophosphorylated to hyperphosphorylated pRb. The expression of cyclin D1 and p27(kip1) were elevated in dl888-infected cells compared to wild-type-infected CV-1 cells. Taken together, these results indicate that small t antigen plays a role in stimulating entry into >G2 in SV40-infected CV-1 cells, possibly by affecting the regulation of key cell cycle proteins.
Whalen
B
B
Department of Microbiology, Immunology, and Molecular Genetics, Albany Medical College, 47 New Scotland Avenue, Albany, New York 12208, USA.
Laffin
J
J
Friedrich
T D
TD
Lehman
J M
JM
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics; D002522:Chlorocebus aethiops; D019938:Cyclin D1 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA / Q000096:biosynthesis; D016195:G2 Phase; D005786:Gene Expression Regulation; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008898:Mimosine / Q000494:pharmacology; D009154:Mutation; D010766:Phosphorylation; D011123:Polyploidy; D016160:Retinoblastoma Protein / Q000032:analysis / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008898:Mimosine; D004247:DNA