Suppression of block to entry into S phase in cell-cycle mutants of rat 3Y1 fibroblasts after transformation by adenovirus type 12.
Four temperature-sensitive (ts) mutants of rat 3Y1 fibroblasts, belonging to separate complementation groups, cease to proliferate in the G1 phase of the cell cycle at a restrictive temperature (39.8 degrees). These ts mutants were transformed at a permissive temperature with adenovirus type 12 (Ad12), its E1A gene, or in203S mutant of Ad12 which has a mutation in the E1A 13 S mRNA unique region. We examined whether the proliferation of the transformed cells would be blocked in the G1 phase, at 39.8 degrees. One mutant did not cease to proliferate at 39.8 degrees after transformation with either Ad12 or E1A. In two other mutants, Ad12-transformed cells did not cease to proliferate at 39.8 degrees, whereas E1A-transformed cells did not survive at 39.8 degrees, though they did continue to enter the S phase. Analysis of transcription of the viral early genes in the transformants of one of the latter two mutants suggests that the expression of other viral early genes, in addition to E1A, is required for cell proliferation, in addition to entry into S phase. In the fourth mutant, both Ad12- and E1A-transformed sublines did not cease to enter the S phase but cells readily detached from the dishes. These results suggest that (1) function(s) of the E1A gene alone is sufficient for Ad12 to suppress the inhibition of the initiation of cellular DNA synthesis caused by four different cellular ts defects, (2) functions of Ad12 early genes other than, or in addition to, E1A are necessary for suppression of the inhibition of cell proliferation (and/or for survival) in two of the four ts mutants, and (3) in the case of one other ts mutant, E1A alone overcomes the ts defect and allows for the entire cell proliferation.
Matsuzaki
A
A
Department of Virology, Kyushu University, Fukuoka, Japan.
Shiroki
K
K
Kimura
G
G
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017456:Adenovirus Early Proteins; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002472:Cell Transformation, Viral; D004261:DNA Replication; D005347:Fibroblasts / Q000502:physiology*; D005814:Genes, Viral; D005816:Genetic Complementation Test; D007399:Interphase; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000502:physiology*; D051381:Rats; D013696:Temperature
D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral