Taking a new TAK on Tat transactivation (original) (raw)

  1. Katherine A. Jones1
  2. The Salk Institute for Biological Studies, La Jolla, California 92037-1099 USA

A common rate-limiting step in the transcription of inducible eukaryotic genes is the release of RNA polymerase II (RNAPII) molecules from stalled elongation complexes that accumulate shortly after the initiation of RNA synthesis (Blair et al. 1996; Blau et al. 1996; for review, see Greenblatt et al. 1993; Bentley 1995). In the absence of the inducer protein, transcription at these genes is usually initiated by RNAP complexes that pause at sites 20–60 nucleotides downstream of the promoter. Promoter–proximal pausing is then counteracted by DNA- or RNA-binding activators that are capable of recruiting or stimulating positive-acting transcription elongation factors. Control at the level of elongation allows for the rapid induction of transcription in response to a specific activator, in part by bypassing the need to assemble stable preinitiation complexes and also by maintaining the promoter in an open conformation that is immediately accessible to regulatory factors.

The induction of the human immunodeficiency virus (HIV-1 and HIV-2) promoters by the essential virus-encoded Tat protein has proven to be a very useful model system for studies of the mechanisms that regulate the assembly and release of early elongation complexes. In this issue of Genes & Development, three exciting new papers provide the strongest evidence to date that the HIV Tat proteins act to target host cell kinases that enhance the processivity of RNAPII at an early elongation step. First, Zhu et al. (this issue) demonstrate that Tat binds with high affinity and specificity to a novel carboxy-terminal domain (CTD) kinase complex, the positive transcriptional elongation factor b (P-TEFb) known to function at an early elongation step, and that the protein kinase responsible for P-TEFb activity is a previously known cdc2-related kinase called PITALRE (Grana et al. 1994; Garriga et al. 1996). Second, Mancebo et al. (this issue) report that …