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ELONGIN AND THE ELONGIN A UBIQUITIN LIGASE COMPLEX IN TRANSCRIPTION AND THE RESPONSE TO DNA DAMAGE
Author(s) -
Conaway Joan W,
Weems Juston C.,
Slaughter Brian D.,
Unruh Jay R.,
Conaway Ronald C.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.252.3
Subject(s) - ubiquitin ligase , ubiquitin , ubiquitin protein ligases , microbiology and biotechnology , biology , dna ligase , cullin , transcription factor , biochemistry , dna , gene
Elongin A performs dual functions in cells as a component of the Elongin ABC complex, a Pol II elongation factor, and as the substrate recognition subunit of an E3 ubiquitin ligase that works in concert with the ubiquitin ligase NEDD4 to target Pol II stalled at sites of DNA damage and other impediments for ubiquitination and degradation by the proteasome. Assembly of the Elongin A ubiquitin ligase proceeds via binding of the Elongin ABC complex to a heterodimer composed of Cullin family member CUL5 AND RING finger protein RBX. We recently discovered that assembly of the Elongin A ubiquitin ligase is a tightly regulated process induced by a wide variety of stimuli and signal transduction pathways. Whereas under normal conditions, the majority of Elongin A is present in cells in the Elongin ABC complex, assembly of the Elongin A ubiquitin ligase is induced by DNA damage and other stresses that lead to accumulation of stalled Pol II. Assembly of the Elongin A ubiquitin ligase is also induced by stimuli known to activate Elongin A‐dependent transcription, such as endoplasmic reticulum and nutrient stress and retinoic signaling. Furthermore, assembly of the Elongin A ubiquitin ligase can be induced by doxycycline in U2OS cells carrying multiple copies of a doxycycline‐inducible transgene, but not in parental U2OS cells, suggesting that transcription activation per se is sufficient to drive ligase assembly. These findings raise the intriguing possibility that the Elongin A ubiquitin ligase might play roles not only as part of a “fail‐safe” mechanism to remove stalled Pol II from genes, but also in normal transcription activation processes. Support or Funding Information This work was supported by National Institutes of Health Grant GM041628, a grant to the Stowers Institute from the Helen Nelson Medical Research Fund at the Greater Kansas City Community Foundation, and by the Stowers Institute for Medical Research.