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The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin tightly associates with CDK9 kinase, and was found to be a major subunit of the transcription elongation factor p-TEFb. The kinase complex containing this cyclin and the elongation factor can interact with, and act as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and was shown to be both necessary and sufficient for full activation of viral transcription. This cyclin and its kinase partner were also found to be involved in the phosphorylation and regulation of the carboxy-terminal domain (CTD) of the largest RNA polymerase II subunit. Activity inhibited by 7SK small nuclear RNA. CDK9 has the intrinsic property to shuttle between nucleus and cytoplasm, and enhanced expression of cyclin T1 promotes its nuclear localization. Cyclin T1 binding to HIV-1 tat is regulated by the differential acetylation of tat. HEXIM1 and HEXIM2 maintain the balance between active and inactive forms of P-TEFb, a heterodimeric complex composed of cyclin-dependent kinase 9 and cyclin T. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. NUFIP and P-TEFb with BRCA1 activate transcription by RNA polymerase II. P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. P-TEFb is a key mediator of Myc activated transcription by stimulating elongation. RNAi-mediated gene silencing of P-TEFb in HeLa cells was not lethal and inhibited Tat transactivation and HIV-1 replication in host cells. Since Tat also binds to this cyclin T1 domain and the association between 7SK RNA/MAQ1 and P-TEFb competes with the binding of Tat to cyclin T1, we speculate that the TAR RNA/Tat lentivirus system has evolved to subvert the cellular 7SK RNA/MAQ1 system. Tat and trans-activation-responsive (TAR) RNA-independent induction of HIV-1 long terminal repeat by this protein requires Sp1. The transcription elongation factor P-TEFb interacts with and phosphorylates Tat-SF1. A histidine-rich stretch in CycT1 was found to direct the transcriptional activity of this P-TEFb complex when tethered artificially to DNA. Chimeras between kinase-inactive mutant Cdk9 and truncated cyclin T1 proteins efficiently inhibit Tat transactivation and human immunodeficiency virus gene expression. Cyclin T1 binds with granulin to inhibit transcription. Downregulation of hCycT1 did not cause apoptotic cell death. Fluctuation in CycT1 levels during human macrophage differentiation may be involved in the regulation of HIV-1 replication. Increased estrogen down regulated gene 1 expression results in inhibition of cyclin T1 recruitment and estrogen receptor 1 DNA binding. Major portion of nuclear P-TEFb is sequestered and inactivated by the coordinated actions of the 7SK snRNA. Recruitment to nuclear bodies via direct interaction with PML protein. Review of work indicating under some circumstances TAK/P-TEFb is likely to be limiting for HIV replication in CD4+ T cells and macrophages; review of mechanisms of regulation of the TAK/P-TEFb subunits in these cell types. The transcriptional repressor PIE-1 from Caenorhabditis elegans binds Cyclin T1 via an alanine-containing heptapeptide repeat and inhibits transcriptional elongation {cyclin T1).
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