The proteasome lid triggers COP9 signalosome activity during the transition of Sachharomyces cerevisiae cells into quiescence

Laylan Bramasole, Abhishek Sinha, Dana Harshuk, Angela Cirigliano, Sylvia Gurevich, Zanlin Yu, Rinat Lift Carmeli, Michael H. Glickman, Teresa Rinaldi, Elah Pick

Research output: Contribution to journalArticlepeer-review


The class of Cullin–RING E3 ligases (CRLs) selectively ubiquitinate a large portion of proteins targeted for proteolysis by the 26S proteasome. Before degradation, ubiquitin molecules are removed from their conjugated proteins by deubiquitinating enzymes, a handful of which are associated with the proteasome. The CRL activity is triggered by modification of the Cullin subunit with the ubiquitin-like protein, NEDD8 (also known as Rub1 in Saccharomyces cerevisiae). Cullin modification is then reversed by hydrolytic action of the COP9 signalosome (CSN). As the NEDD8–Rub1 catalytic cycle is not essential for the viability of S. cerevisiae, this organism is a useful model system to study the alteration of Rub1–CRL conjugation patterns. In this study, we describe two distinct mutants of Rpn11, a proteasome-associated deubiquitinating enzyme, both of which exhibit a biochemical phenotype characterized by high accumulation of Rub1-modified Cdc53–Cullin1 (yCul1) upon entry into quiescence in S. cerevisiae. Further characterization revealed proteasome 19S-lid-associated deubiquitination activity that authorizes the hydrolysis of Rub1 from yCul1 by the CSN complex. Thus, our results suggest a negative feedback mechanism via proteasome capacity on upstream ubiquitinating enzymes.

Original languageEnglish
Article number449
Issue number9
StatePublished - Sep 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


  • 26S proteasome
  • Budding yeast
  • CSN (COP9 signalosome)
  • Cdc53
  • Cullin
  • Diauxic shift
  • NEDD8 (neural precursor cell expressed developmentally down-regulated 8)
  • Proteasome lid
  • Rpn11
  • Rub1 (Related ubiquitin 1)
  • SCF (Skp, Cullin, F-box containing complex)
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


Dive into the research topics of 'The proteasome lid triggers COP9 signalosome activity during the transition of Sachharomyces cerevisiae cells into quiescence'. Together they form a unique fingerprint.

Cite this