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Title:A Role for Oligomerization in the Multifunctional Nature of the Simian Virus 40 Large T Antigen Protein (Tumor, Dna, Cell Transformation, Association)
Author(s):So, Lorna Cecilia Y.
Department / Program:Biochemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Biology, Molecular
Health Sciences, Immunology
Abstract:Simian virus 40 (SV40) large T antigen protein plays a central role in the interaction of the virus with its host. It is required for both the growth of the virus in permissive hosts and in the transformation of non-permissive hosts to a tumorigenic phenotype. Biochemical studies reveal that large T antigen has several activities detectable in vitro. While the multifunctional nature of this protein is already generally accepted, the structural basis for this behavior remains unknown. In this thesis, we obtain some insight into the involvement of oligomerization by addressing the question of whether selected in vitro activities are affected by the molecular size of the protein. Large T antigen protein has isolated from a line of SV40 virus-transformed human fibroblast cells called SV80. Using high performance size exclusion chromatography, the purified protein was found to consist of a mixture of aggregate and monomeric forms whose distribution can be easily perturbed. Increasing the dilution of the protein and the sample ionic strength resulted in dissociation of the aggregate form whereas addition of hydrolyzable nucleotide triphosphates resulted in reassociation of the monomer. This reassociation reaction was found to be closely linked to the phosphorylation of large T antigen by kinase activity endogenous to the preparation. Both the ATP hydrolysing and DNA binding activities of large T antigen were higher at assay conditions favoring the formation and maintenance of the aggregate form. Our results and reports that the specific binding of large T antigen to the SV40 virus origin of viral DNA replication is mediated by the monomeric form of the protein suggest that distinct forms of the protein carryout its various functions. The implications of this hypothesis to the interesting question of how the large T antigen protein effects the tumorigenic transformation of cells in vitro are discussed.
Issue Date:1986
Description:203 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1986.
Other Identifier(s):(UMI)AAI8610981
Date Available in IDEALS:2014-12-15
Date Deposited:1986

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