ELA1 and CUL3 are required along with ELC1 for RNA polymerase II polyubiquitylation and degradation in DNA-damaged yeast cells.
Treatment of yeast and human cells with DNA-damaging agents elicits lysine 48-linked polyubiquitylation of Rpb1, the largest subunit of RNA polymerase II (Pol II), which targets Pol II for proteasomal degradation. However, the ubiquitin ligase (E3) responsible for Pol II polyubiquitylation has not been identified in humans or the yeast Saccharomyces cerevisiae. Here we show that elongin A (Ela1) and cullin 3 (Cul3) are required for Pol II polyubiquitylation and degradation in yeast cells, and on the basis of these and other observations, we propose that an E3 comprised of elongin C (Elc1), Ela1, Cul3, and the RING finger protein Roc1 (Rbx1) mediates this process in yeast cells. This study provides, in addition to the identification of the E3 required for Pol II polyubiquitylation and degradation in yeast cells, the first evidence for a specific function in yeast for a member of the elongin C/BC-box protein/cullin family of ligases. Also, these observations raise the distinct possibility that the elongin C-containing ubiquitin ligase, the von Hippel-Lindau tumor suppressor complex, promotes Pol II polyubiquitylation and degradation in human cells.
Ribar
Balazs
B
University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555-1061, USA.
Prakash
Louise
L
Prakash
Satya
S
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D044842:Cullin Proteins / Q000378:metabolism*; D004249:DNA Damage; D000075065:Elongin; D009154:Mutation / Q000235:genetics; D025821:Polyubiquitin / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000528:radiation effects; D015363:Quinolones / Q000494:pharmacology; D012319:RNA Polymerase II / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014466:Ultraviolet Rays
C120195:4-nitroquinolone-1-oxide; C480739:CUL3 protein, S cerevisiae; D044842:Cullin Proteins; C000616397:ELOA protein, human; C000616395:ELOC protein, human; D000075065:Elongin; D015363:Quinolones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025821:Polyubiquitin; D015112:4-Nitroquinoline-1-oxide; D012319:RNA Polymerase II; C511736:RPB1 protein, S cerevisiae