title: Assembly of the Elongin A Ubiquitin Ligase Is Regulated by Genotoxic and Other Stresses.
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.
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors: Juston C
authors: JC
authors: Weems
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors: Brian D
authors: BD
authors: Slaughter
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors: Jay R
authors: JR
authors: Unruh
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors: Shawn M
authors: SM
authors: Hall
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors: Merry B
authors: MB
authors: McLaird
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors: Joshua M
authors: JM
authors: Gilmore
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110, the Departments of Pathology and Laboratory Medicine and.
authors: Michael P
authors: MP
authors: Washburn
authors: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors: Laurence
authors: L
authors: Florens
authors: the Department of Functional Genomics, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
authors: Takashi
authors: T
authors: Yasukawa
authors: the Department of Functional Genomics, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
authors: Teijiro
authors: T
authors: Aso
authors: 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.
authors: Joan W
authors: JW
authors: Conaway
authors: 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.
authors: Ronald C
authors: RC
authors: Conaway
mesh_terms: D000075065:Elongin; D031541:Fluorescence Resonance Energy Transfer; D019084:Fluorescent Antibody Technique, Indirect; D057809:HEK293 Cells; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: C000616397:ELOA protein, human; D000075065:Elongin; D009153:Mutagens; D012333:RNA, Messenger; D014157:Transcription Factors; D014212:Tretinoin; D044767:Ubiquitin-Protein Ligases
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