Abstract
The 26S proteasome recognizes a vast number of ubiquitin-dependent degrada tion signals linked to various substrates. This recognition is mediated mainly by the stoichio metric proteasomal resident ubiquitin receptors S5a and Rpn13, which harbor ubiquitin-bind ing domains. Regulatory steps in substrate binding, processing, and subsequent downstream proteolytic events by these receptors are poorly understood. Here we demonstrate that mammalian S5a is present in proteasome-bound and free states. S5a is required for efficient proteasomal degradation of polyubiquitinated substrates and the recruitment of ubiquitin- like (Ubl) harboring proteins; however, S5a-mediated ubiquitin and Ubl binding occurs only on the proteasome itself. We identify the VWA domain of S5a as a domain that limits ubiq uitin and Ubl binding to occur only upon proteasomal association. Multiubiquitination events within the VWA domain can further regulate S5a association. Our results provide a molecular explanation to how ubiquitin and Ubl binding to S5a is restricted to the 26S proteasome.
Original language | English |
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Pages (from-to) | 3988-3998 |
Number of pages | 11 |
Journal | Molecular Biology of the Cell |
Volume | 25 |
Issue number | 25 |
DOIs | |
State | Published - 15 Dec 2014 |
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
- General Medicine