AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation

Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):E15-24. doi: 10.1073/pnas.1318503111. Epub 2013 Dec 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Cell Cycle Proteins
  • Cell Nucleus / metabolism
  • Cyclin T / chemistry*
  • Cyclin-Dependent Kinase 9 / chemistry
  • DNA-Binding Proteins / physiology*
  • HeLa Cells
  • Humans
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / physiology*
  • Positive Transcriptional Elongation Factor B / chemistry*
  • Protein Binding
  • Protein Structure, Tertiary
  • Ribonucleoproteins, Small Nuclear / chemistry*
  • Transcription Factors / chemistry
  • Transcriptional Activation
  • Transcriptional Elongation Factors
  • tat Gene Products, Human Immunodeficiency Virus / genetics*


  • BRD4 protein, human
  • CCNT1 protein, human
  • Cell Cycle Proteins
  • Cyclin T
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Ribonucleoproteins, Small Nuclear
  • Transcription Factors
  • Transcriptional Elongation Factors
  • tat Gene Products, Human Immunodeficiency Virus
  • AFF1 protein, human
  • Positive Transcriptional Elongation Factor B
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9
  • Alanine