title: AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation.
abstract: The positive transcription elongation factor b (P-TEFb) stimulates RNA polymerase elongation by inducing the transition of promoter proximally paused polymerase II into a productively elongating state. P-TEFb itself is regulated by reversible association with various transcription factors/cofactors to form several multisubunit complexes [e.g., the 7SK small nuclear ribonucleoprotein particle (7SK snRNP), the super elongation complexes (SECs), and the bromodomain protein 4 (Brd4)-P-TEFb complex] that constitute a P-TEFb network controlling cellular and HIV transcription. These complexes have been thought to share no components other than the core P-TEFb subunits cyclin-dependent kinase 9 (CDK9) and cyclin T (CycT, T1, T2a, and T2b). Here we show that the AF4/FMR2 family member 1 (AFF1) is bound to CDK9-CycT and is present in all major P-TEFb complexes and that the tripartite CDK9-CycT-AFF1 complex is transferred as a single unit within the P-TEFb network. By increasing the affinity of the HIV-encoded transactivating (Tat) protein for CycT1, AFF1 facilitates Tat's extraction of P-TEFb from 7SK snRNP and the formation of Tat-SECs for HIV transcription. Our data identify AFF1 as a ubiquitous P-TEFb partner and demonstrate that full Tat transactivation requires the complete SEC.
authors.affiliation: School of Pharmaceutical Sciences, Innovation Center for Cell Biology, Xiamen University, Xiamen 361005, Fujian, China.
authors.forename: Huasong
authors.initials: H
authors.lastname: Lu
authors.forename: Zichong
authors.initials: Z
authors.lastname: Li
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Xue
authors.forename: Ursula
authors.initials: U
authors.lastname: Schulze-Gahmen
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.forename: Tom
authors.initials: T
authors.lastname: Alber
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000409:Alanine / Q000235:genetics; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D056906:Cyclin T / Q000737:chemistry*; D042863:Cyclin-Dependent Kinase 9 / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D042925:Positive Transcriptional Elongation Factor B / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
chemical_list: D000409:Alanine; D018797:Cell Cycle Proteins; D056906:Cyclin T; D042863:Cyclin-Dependent Kinase 9; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D042925:Positive Transcriptional Elongation Factor B; D017411:Ribonucleoproteins, Small Nuclear; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C503684:CCNT1 protein, human; C081449:AFF1 protein, human; C467969:CDK9 protein, human