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J. Biol. Chem., Vol. 259, Issue 19, 11777-11783, 10, 1984
T Subramanian, M Kuppuswamy, J Gysbers, S Mak and G Chinnadurai
The adenovirus E1b region (mp 4.5-11.2) codes for two major tumor antigens
of 53 and 19 kDa. The lp+ locus maps within the 19-kDa tumor antigen-coding
region and has been shown to play an essential role in cell transformation.
We have investigated the role of the 19-kDa tumor antigen during productive
virus growth using a specific Ad2 mutant (dl250) lacking most of the 19-kDa
tumor antigen-coding region. Mutant dl250 grows more slowly and yields
about 100-fold less progeny virus than Ad2 wt in human KB cells. In cells
infected with mutant dl250, viral DNA is present at only about one-half the
level of that of Ad2 wt. The defect in DNA accumulation appears to be both
at the level of DNA synthesis and stability of newly synthesized DNA. In
mutant- infected cells, newly replicated viral as well as cellular DNA are
extensively degraded during late stages of viral infection. We have mapped
a class of Ad12 (highly oncogenic group A) mutants (cyt) that are
nononcogenic in newborn hamsters and induce DNA degradation to the 19-kDa
tumor antigen-coding region by intertypic complementation analysis. These
results strongly suggest that the 19-kDa tumor antigen plays an essential
role in efficient viral DNA synthesis and protection of newly replicated
viral DNA against cellular nucleases in addition to its role in cell
transformation and tumorigenesis.
19-kDa tumor antigen coded by early region E1b of adenovirus 2 is required for efficient synthesis and for protection of viral DNA
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