A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling.
Protein degradation, chromatin remodeling, and membrane trafficking are critically regulated by ubiquitylation. The presence of several coexisting ubiquitin-dependent processes, each of crucial importance to the cell, is remarkable. This brings up questions on how the usage of this versatile regulator is negotiated between the different cellular processes. During proteotoxic stress, the accumulation of ubiquitylated substrates coincides with the depletion of ubiquitylated histone H2A and chromatin remodeling. We show that this redistribution of ubiquitin during proteotoxic stress is a direct consequence of competition for the limited pool of free ubiquitin. Thus, the ubiquitin cycle couples various ubiquitin-dependent processes because of a rate-limiting pool of free ubiquitin. We propose that this ubiquitin equilibrium may allow cells to sense proteotoxic stress in a genome-wide fashion.
Dantuma
Nico P
NP
Department of Cell and Molecular Biology, The Medical Nobel Institute, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Groothuis
Tom A M
TA
Salomons
Florian A
FA
Neefjes
Jacques
J
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D005656:Fungal Proteins; D006657:Histones; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex