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.
Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya, Japan. kimura-yk@igakuken.or.jp
Yoko
Y
Kimura
Hideki
H
Yashiroda
Tai
T
Kudo
Sumiko
S
Koitabashi
Shigeo
S
Murata
Akira
A
Kakizuka
Keiji
K
Tanaka
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