Format

Send to

Choose Destination
J Biol Chem. 2015 Jun 12;290(24):15030-41. doi: 10.1074/jbc.M114.632794. Epub 2015 Apr 15.

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

Author information

1
From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
2
From the Stowers Institute for Medical Research, Kansas City, Missouri 64110, the Departments of Pathology and Laboratory Medicine and.
3
the Department of Functional Genomics, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
4
From the Stowers Institute for Medical Research, Kansas City, Missouri 64110, Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, and jlc@stowers.org.
5
From the Stowers Institute for Medical Research, Kansas City, Missouri 64110, Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, and rcc@stowers.org.

Abstract

Elongin A performs dual functions in cells as a component of RNA polymerase II (Pol II) transcription elongation factor Elongin and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase that has been shown to target Pol II stalled at sites of DNA damage. Here we investigate the mechanism(s) governing conversion of the Elongin complex from its elongation factor to its ubiquitin ligase form. We report the discovery that assembly of the Elongin A ubiquitin ligase is a tightly regulated process. In unstressed cells, Elongin A is predominately present as part of Pol II elongation factor Elongin. Assembly of Elongin A into the ubiquitin ligase is strongly induced by genotoxic stress; by transcriptional stresses that lead to accumulation of stalled Pol II; and by other stimuli, including endoplasmic reticulum and nutrient stress and retinoic acid signaling, that activate Elongin A-dependent transcription. Taken together, our findings shed new light on mechanisms that control the Elongin A ubiquitin ligase and suggest that it may play a role in Elongin A-dependent transcription.

KEYWORDS:

RNA polymerase II; confocal microscopy; endoplasmic reticulum stress (ER stress); fluorescence resonance energy transfer (FRET); gene transcription; stress response; transcription elongation factor; ubiquitin ligase

PMID:
25878247
PMCID:
PMC4463447
DOI:
10.1074/jbc.M114.632794
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center