Linked Life Data

8122368

Source:http://linkedlifedata.com/resource/pubmed/id/8122368

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-4-4
pubmed:abstractText
Two sets of mutations were introduced into a region of the JC virus (JCV) large tumor (T) antigen involved in binding the retinoblastoma susceptibility gene product (Rb). The first set converted the JCV sequences to those found in the corresponding region of the simian virus 40 (SV40) T antigen. The second set contained sequence changes predicted to abolish Rb binding. Each of these mutations was also inserted into a chimeric T antigen (MSTn) composed of JCV and SV40 sequences at its amino- and carboxy termini, respectively. The JCV T antigen is less efficient than its SV40 counterpart at transforming Rat2 cells and at binding Rb and viral DNA. These activities were altered in the two sets of mutants generated in this study. A JCV T antigen mutant having an SV40-like Rb-binding domain exhibited increased DNA binding activity while, unexpectedly, displaying decreased Rb binding and wild-type transforming behavior. A mutant T antigen that was unable to bind Rb exhibited decreased DNA binding and failed to transform Rat2 cells. Both mutants were defective for DNA replication and did not produce infectious virions. Additional phenotypic changes were observed when each mutation was introduced into the chimeric MSTn T antigen. As the oligomerization state of SV40 T antigen is known to influence several of its activities, including Rb binding, the quaternary structure of the T proteins used in this study was assessed by sucrose gradient sedimentation. The SV40 and chimeric MSTn T antigen sedimented as a mixture of monomers/dimers and higher oligomers, whereas the JCV T antigen sedimented predominantly as monomers/dimers; neither mutation in the T antigen Rb-binding motif affected the sedimentation profiles of the parental T proteins. Restricted biochemical activity of the JCV T protein relative to that of SV40 supports the suggestion that this regulatory protein contributes to the attenuation of the JCV lytic cycle.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:volume
199
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
384-92
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Converting the JCV T antigen Rb binding domain to that of SV40 does not alter JCV's limited transforming activity but does eliminate viral viability.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.