Transcriptional properties of mammalian elongin A and its role in stress response.

Elongin A was shown previously to be capable of potently activating the rate of RNA polymerase II (RNAPII) transcription elongation in vitro by suppressing transient pausing by the enzyme at many sites along DNA templates. The role of Elongin A in RNAPII transcription in mammalian cells, however, has not been clearly established. In this report, we investigate the function of Elongin A in RNAPII transcription.

Functional characterization of a mammalian transcription factor, Elongin A.

Elongin A is the transcriptionally active subunit of the Elongin complex that strongly stimulates the rate of elongation by RNA polymerase II (pol II) by suppressing the transient pausing of the polymerase at many sites along the DNA template. We have recently shown that Elongin A-deficient mice are embryonic lethal, and mouse embryonic fibroblasts (MEFs) derived from Elongin A(-/-) embryos display not only increased apoptosis but also senescence-like phenotypes accompanied by the activation of p53. To further understand the function of Elongin A in vivo, we have carried out the structure-function analysis of Elongin A and identified sequences critical to its nuclear localization and direct interaction with pol II.

A splice variant of stress response gene ATF3 counteracts NF-kappaB-dependent anti-apoptosis through inhibiting recruitment of CREB-binding protein/p300 coactivator.

Activating transcription factor (ATF) 3 plays a role in determining cell fate and generates a variety of alternatively spliced isoforms in stress response. We have reported previously that splice variant ATF3deltaZip2, which lacks the leucine zipper region, is induced in response to various stress stimuli. However, its biological function has not been elucidated.