Identification of a region of simian virus 40 large T antigen required for cell transformation.
A series of replication-competent simian virus 40 (SV40) large T antigens with point and deletion mutations in the amino acid sequence between residues 105 and 115 were examined for the ability to immortalize primary cultures of mouse and rat cells. The results show that certain mutants, including one that deletes the entire region, are able to immortalize. However, consistent with previous data, the immortalized cells are not fully transformed, as judged by doubling time, sensitivity to concentrations of serum, and anchorage-independent growth. The region from 106 to 114 has structural features in common with a region involved in transformation by adenovirus E1a protein (J. Figge, T. Webster, T.F. Smith, and E. Paucha, J. Virol. 62:1814-1818, 1988) and influences the binding of the retinoblastoma gene product to large T (J.A. DeCaprio, J.W. Ludlow, J. Figge, J.-Y. Shew, C.-M. Huang, W.-H. Lee, E. Marsilio, E. Paucha, and D.M. Livingston, Cell 54:275-283, 1988). Together, these results imply that the sequence from 106 to 114 forms part of a domain that is essential for transformation of established cells, is dispensable for immortalization, and is not required for SV40 replication. The results also indicate that the ability of SV40 large T to immortalize primary cells is independent of its ability to bind to the retinoblastoma gene product.
Chen
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S
Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Boston, Massachusetts.
Paucha
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E
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002455:Cell Division; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D015870:Gene Expression; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D016160:Retinoblastoma Protein; D013539:Simian virus 40 / Q000472:pathogenicity*; D013329:Structure-Activity Relationship; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D010750:Phosphoproteins; D016160:Retinoblastoma Protein