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PMID: 9990016 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T.

Fujinaga K, Taube R, Wimmer J, Cujec TP, Peterlin BM

Abstract

The transcriptional transactivator Tat from HIV binds to the transactivation response element (TAR) RNA to increase rates of elongation of viral transcription. Human cyclin T supports these interactions between Tat and TAR. In this study, we report the sequence of mouse cyclin T and identify the residues from positions 1 to 281 in human cyclin T that bind to Tat and TAR. Mouse cyclin T binds to Tat weakly and is unable to facilitate interactions between Tat and TAR. Reciprocal exchanges of the cysteine and tyrosine at position 261 in human and mouse cyclin T proteins also render human cyclin T inactive and mouse cyclin T active. These findings reveal the molecular basis for the restriction of Tat transactivation in rodent cells.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution Animals CHO Cells Chloramphenicol O-Acetyltransferase/metabolism Cricetinae Cyclin T Cyclins/chemistry,genetics,metabolism Cysteine Gene Products, tat/metabolism HIV Long Terminal Repeat/physiology Humans Mice Molecular Sequence Data Mutagenesis, Site-Directed Recombinant Fusion Proteins/metabolism Recombinant Proteins/chemistry,metabolism Sequence Alignment Sequence Homology, Amino Acid Tyrosine
Chemicals
CCNT1 protein, human Ccnt1 protein, mouse Cyclin T Cyclins Gene Products, tat Recombinant Fusion Proteins Recombinant Proteins Tyrosine Chloramphenicol O-Acetyltransferase Cysteine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Fujinaga K
Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, CA 94143-0703, USA.
Taube R
Wimmer J
Cujec T P
Peterlin B M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-02-16
Pages
1285-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15455
Subset
IM
Databases
GENBANK
AF113951
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