VWA domain of S5a restricts the ability to bind ubiquitin and Ubl to the 26S proteasome

Ravit Piterman, Ilana Braunstein, Elada Isakov, Tamar Ziv, Ami Navon, Shenhav Cohen, Ariel Stanhill

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)3988-3998
Number of pages11
JournalMolecular Biology of the Cell
Issue number25
StatePublished - 15 Dec 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Piterman Braunstein Isakov et al.


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