FBI-1 Can Stimulate HIV-1 Tat Activity and Is Targeted to a Novel Subnuclear Domain that Includes the Tat-P-TEFb—containing Nuclear Speckles
Copyright policy )FBI-1 Can Stimulate HIV-1 Tat Activity and Is Targeted to a Novel Subnuclear Domain that Includes the Tat-P-TEFb—containing Nuclear Speckles
FBI-1 is a cellular POZ-domain–containing protein that binds to the HIV-1 LTR and associates with the HIV-1 transactivator protein Tat. Here we show that elevated levels of FBI-1 specifically stimulate Tat activity and that this effect is dependent on the same domain of FBI-1 that mediates Tat-FBI-1 association in vivo. FBI-1 also partially colocalizes with Tat and Tat's cellular cofactor, P-TEFb (Cdk9 and cyclin T1), at the splicing-factor–rich nuclear speckle domain. Further, a less-soluble population of FBI-1 distributes in a novel peripheral-speckle pattern of localization as well as in other nuclear regions. This distribution pattern is dependent on the FBI-1 DNA binding domain, on the presence of cellular DNA, and on active transcription. Taken together, these results suggest that FBI-1 is a cellular factor that preferentially associates with active chromatin and that can specifically stimulate Tat-activated HIV-1 transcription.
- Howard Hughes Medical Institute United States
- Northwestern State University United States
- Cold Spring Harbor Laboratory United States
Cell Nucleus, Transcription, Genetic, Cyclin T, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinase 9, Cyclin-Dependent Kinases, Protein Structure, Tertiary, DNA-Binding Proteins, Genes, Reporter, Cyclins, Gene Products, tat, Humans, Nucleic Acid Conformation, Positive Transcriptional Elongation Factor B, Promoter Regions, Genetic, HeLa Cells, Transcription Factors
Cell Nucleus, Transcription, Genetic, Cyclin T, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinase 9, Cyclin-Dependent Kinases, Protein Structure, Tertiary, DNA-Binding Proteins, Genes, Reporter, Cyclins, Gene Products, tat, Humans, Nucleic Acid Conformation, Positive Transcriptional Elongation Factor B, Promoter Regions, Genetic, HeLa Cells, Transcription Factors
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