Mammalian Elongin A complex mediates DNA-damage-induced ubiquitylation and degradation of Rpb1

The Elongin complex stimulates the rate of transcription elongation by RNA polymerase II (pol II) by suppressing transient pausing of the pol II at many sites along the DNA. Elongin is composed of a transcriptionally active A subunit and two small regulatory B and C subunits, which can form an isola...

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Bibliographic Details
Published in:The EMBO journal 2008-12, Vol.27 (24), p.3256-3266
Main Authors: Yasukawa, Takashi, Kamura, Takumi, Kitajima, Shigetaka, Conaway, Ronald C, Conaway, Joan W, Aso, Teijiro
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cullin
Cullin Proteins - metabolism
Deoxyribonucleic acid
DNA
DNA Damage
E3 ubiquitin ligase
Elongin
Humans
Irradiation
Mammals
Molecular biology
Protein Binding
Proteins
RNA polymerase
RNA polymerase II
RNA Polymerase II - metabolism
transcription elongation
Transcription Factors - metabolism
Ubiquitination
Ultraviolet radiation
Ultraviolet Rays
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Summary:The Elongin complex stimulates the rate of transcription elongation by RNA polymerase II (pol II) by suppressing transient pausing of the pol II at many sites along the DNA. Elongin is composed of a transcriptionally active A subunit and two small regulatory B and C subunits, which can form an isolable Elongin BC subcomplex. Here, we have shown that both the ubiquitylation and proteasomal degradation of the largest subunit of pol II (Rpb1) following UV‐irradiation are significantly suppressed in Elongin A‐deficient cells; however, in both cases suppression is rescued by transfection of wild‐type Elongin A. Moreover, we have demonstrated that the Elongin A–Elongin BC complex is capable of assembling with the Cul5/Rbx2 module, and that this hetero‐pentamer complex efficiently ubiquitylates Rpb1 in vitro . Mechanistic studies indicate that colocalization of Elongin A and Cul5 in cells and the interaction of Elongin A with the Ser5‐phosphorylated form of Rpb1 are strongly enhanced following UV‐irradiation. Taken together, our results suggest that mammalian Elongin A is directly involved in ubiquitylation and degradation of Rpb1 following DNA damage.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2008.249