Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2002-6-24
pubmed:databankReference
pubmed:abstractText
Human immunodeficiency virus type 1 (HIV-1) gene expression and replication is highly dependent on and modulated by interactions between viral and host cellular factors. Tat protein, encoded by one of the HIV-1 regulatory genes, tat, is essential for HIV-1 gene expression. A number of host cellular factors have been shown to interact with Tat in this process. During our attempts to determine the molecular mechanisms of Tat interaction with brain cells, we isolated a cDNA clone that encodes a novel Tat-interacting protein of 110 kDa or Tip110 from a human fetal brain cDNA library. GenBank BLAST search revealed that Tip110 was almost identical to a previously cloned KIAA0156 gene with unknown functions. In vivo binding of Tip110 with Tat was confirmed by immunoprecipitation and Western blotting, in combination with mutagenesis. The yeast three-hybrid RNA-protein interaction assay indicated no direct interaction of Tip110 with Tat transactivating response element RNA. Nevertheless, Tip110 strongly synergized with Tat on Tat-mediated chloramphenicol acetyltransferase reporter gene expression and HIV-1 virus production, whereas down-modulation of constitutive Tip110 expression inhibited HIV-1 virus production. Northern blot analysis showed that Tip110 mRNA was expressed in a variety of human tissues and cells. Moreover, digital fluorescence microscopic imaging revealed that Tip110 was expressed exclusively in the nucleus, and within a nuclear speckle structure that has recently been described for human cyclin T and CDK9, two critical components for Tat transactivation function on HIV-1 long terminal repeat promoter. Taken together, these data demonstrate that Tip110 regulates Tat transactivation activity through direct interaction, and suggest that Tip110 is an important cellular factor for HIV-1 gene expression and viral replication.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23854-63
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11959860-Amino Acid Sequence, pubmed-meshheading:11959860-Antigens, Neoplasm, pubmed-meshheading:11959860-Cell Line, pubmed-meshheading:11959860-DNA, Complementary, pubmed-meshheading:11959860-Gene Expression Regulation, Viral, pubmed-meshheading:11959860-Gene Products, tat, pubmed-meshheading:11959860-HIV Long Terminal Repeat, pubmed-meshheading:11959860-HIV-1, pubmed-meshheading:11959860-Humans, pubmed-meshheading:11959860-Molecular Sequence Data, pubmed-meshheading:11959860-Molecular Weight, pubmed-meshheading:11959860-Nuclear Proteins, pubmed-meshheading:11959860-Promoter Regions, Genetic, pubmed-meshheading:11959860-RNA, Messenger, pubmed-meshheading:11959860-RNA-Binding Proteins, pubmed-meshheading:11959860-Trans-Activators, pubmed-meshheading:11959860-Transcriptional Activation, pubmed-meshheading:11959860-Viral Proteins, pubmed-meshheading:11959860-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2002
pubmed:articleTitle
HIV-1 Tat protein-mediated transactivation of the HIV-1 long terminal repeat promoter is potentiated by a novel nuclear Tat-interacting protein of 110 kDa, Tip110.
pubmed:affiliation
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.