An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis.
The dynamic and reversible process of ubiquitin modification controls various cellular activities. Ubiquitin exists as monomers, unanchored chains, or protein-conjugated forms, but the regulation of these interconversions remains largely unknown. Here, we identified a protein designated Rfu1 (regulator of free ubiquitin chains 1), which regulates intracellular concentrations of monomeric ubiquitins and free ubiquitin chains in Saccharomyces cerevisiae. Rfu1 functions as an inhibitor of Doa4, a deubiquitinating enzyme. Rapid loss of free ubiquitin chains upon heat shock, a condition in which more proteins require ubiquitin conjugation, was mediated in part by Doa4 and Rfu1. Thus, regulation of ubiquitin homeostasis is controlled by a balance between a deubiquitinating enzyme and its inhibitor. We propose that free ubiquitin chains function as a ubiquitin reservoir that allows maintenance of monomeric ubiquitins at adequate levels under normal conditions and rapid supply for substrate conjugation under stress conditions.
Kimura
Yoko
Y
Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya, Japan. kimura-yk@igakuken.or.jp
Yashiroda
Hideki
H
Kudo
Tai
T
Koitabashi
Sumiko
S
Murata
Shigeo
S
Kakizuka
Akira
A
Tanaka
Keiji
K
D000494:Allosteric Regulation; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
C084434:DOA4 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; C542553:Rfu1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex