A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA.
The HIV-1 Tat protein regulates transcription elongation through binding to the viral TAR RNA stem-loop structure. We have isolated a novel 87 kDa cyclin C-related protein (cyclin T) that interacts specifically with the transactivation domain of Tat. Cyclin T is a partner for CDK9, an RNAPII transcription elongation factor. Remarkably, ... the interaction of Tat with cyclin T strongly enhances the affinity and specificity of the Tat:TAR RNA interaction, and confers a requirement for sequences in the loop of TAR that are not recognized by Tat alone. Moreover, overexpression of human cyclin T rescues Tat activity in nonpermissive rodent cells. We propose that Tat directs cyclin T-CDK9 to RNAPII through cooperative binding to TAR RNA.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Bacterial Proteins, CHO Cells, Cell Nucleus, Chemoreceptor Cells, Cloning, Molecular, Cricetinae, Cyclin C, Cyclin T, Cyclin-Dependent Kinases, Cyclins, DNA Footprinting, Escherichia coli Proteins, Gene Expression Regulation, Viral, Gene Products, tat, HIV-1, Humans, Membrane Proteins, Mice, Molecular Sequence Data, Nucleic Acid Conformation, Positive Transcriptional Elongation Factor B, Protein-Serine-Threonine Kinases, RNA Polymerase II, RNA, Viral, Receptors, Cell Surface, Recombinant Proteins, Ribonucleases, Substrate Specificity, Transcription, Genetic, tat Gene Products, Human Immunodeficiency Virus
3T3 Cells, Amino Acid Sequence, Animals, Bacterial Proteins, CHO Cells, Cell Nucleus, Chemoreceptor Cells, Cloning, Molecular, Cricetinae, Cyclin C, Cyclin T, Cyclin-Dependent Kinases, Cyclins, DNA Footprinting, Escherichia coli Proteins, Gene Expression Regulation, Viral, Gene Products, tat, HIV-1, Humans, Membrane Proteins, Mice, Molecular Sequence Data, Nucleic Acid Conformation, Positive Transcriptional Elongation Factor B, Protein-Serine-Threonine Kinases, RNA Polymerase II, RNA, Viral, Receptors, Cell Surface, Recombinant Proteins, Ribonucleases, Substrate Specificity, Transcription, Genetic, tat Gene Products, Human Immunodeficiency Virus
Cell
Date: Feb. 20, 1998
PubMed ID: 9491887
View in: Pubmed Google Scholar
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