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

Takashi Yasukawa, Takumi Kamura, Shigetaka Kitajima, Ronald C. Conaway, Joan W. Conaway, Teijiro Aso

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3256-3266
Number of pages11
JournalEMBO Journal
Volume27
Issue number24
DOIs
StatePublished - Dec 17 2008
Externally publishedYes

Keywords

  • Cullin
  • E3 ubiquitin ligase
  • Elongin
  • RNA polymerase II
  • Transcription elongation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'Mammalian Elongin A complex mediates DNA-damage-induced ubiquitylation and degradation of Rpb1'. Together they form a unique fingerprint.

Cite this