Transcriptional Properties of Mammalian Elongin A and Its Role in Stress Response

Abstract

Background: Transcriptional elongation is a rate-limiting step in activation of stress response genes. Results: Optimal expression of stress response regulator ATF3 requires the elongation activity but not the ubiquitination activity of Elongin A. Conclusion: Elongin A plays a key role for the adequate expression of ATF3 in vivo. Significance: RNAPII ubiquitination and transcriptional elongation are independent activities of Elongin A.

Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription

“…Methylation of EloA is needed for appropriate gene regulation by PRC2 in ES cells and for proper differentiation of ES cells. As EloA interacts with the CTD of RNA Polymerase II (Kawauchi et al, 2013), we propose that regulation occurs by a methylation induced alteration in the ability of EloA to impact transcription via the general transcription machinery. This results in increased downregulation of a subset of PRC2 targets, most of which are already expressed at low levels in WT cells.…”

“…This Elongin complex interacts with the phosphorylated form of Pol II C-terminal domain (CTD) and stimulates transcription elongation (Aso et al, 1996; Kawauchi et al, 2013). The complex is also part of a ubiquitin ligase complex along with Cullin5 and Rbx2 that drives degradation of stalled Pol II (Wilson et al, 2013).…”

Assembly of the Elongin A Ubiquitin Ligase Is Regulated by Genotoxic and Other Stresses

“…Although our data raise the possibility that the Elongin A ubiquitin ligase might contribute to gene activation, it is important to emphasize that ligase-independent functions of Elongin are also likely to be important in this process, because transcription defects in Elongin A (Ϫ/Ϫ) or Elongin A knockdown cells can be rescued in whole or in part by Elongin A mutants that can stimulate Pol II elongation in vitro but do not support efficient Rpb1 ubiquitylation (10,11). Future studies investigating in more detail the biochemical mechanism(s) underlying regulation of assembly of the Elongin A ubiquitin ligase, the signals responsible for its induction, and the potential role of the ligase in Pol II transcription activation will be needed to resolve these issues.…”

“…Elongin C is similar in sequence to the SCF ubiquitin ligase subunit Skp1, whereas Elongin B is a ubiquitin-like protein (5,6). Elongin A has been implicated in activation of Pol II transcription in response to a variety of signals, including retinoic acid, ecdysone, notch, EGF, and TGF-␤, as well as stresses, such as heat shock, DNA damage, nutrient deprivation, and endoplasmic reticulum (ER) stress (7)(8)(9)(10)(11)(12). In at least some cases, Elongin A is thought to function in the release of promoterproximally paused Pol II (9).…”

Induction of p21CIP1 Protein and Cell Cycle Arrest after Inhibition of Aurora B Kinase Is Attributed to Aneuploidy and Reactive Oxygen Species

“…One example of a gene that is activated in a p38-dependent manner is ATF3, which known to be regulated at the level of transcriptional elongation in response to stress (43). It was reported that transcriptional elongation of ATF3 depends on Elongin A, a subunit of a multimeric complex that activates elongation by mammalian RNA Polymerase II (44).…”