TY - JOUR T1 - Rpn1 and Rpn2 coordinate ubiquitin processing factors at the proteasome JF - Journal of Biological ChemistryJ. Biol. Chem. Y1 - 2012 A1 - Rosenzweig,Rina A1 - Bronner,Vered A1 - Zhang,Daoning A1 - Fushman, David A1 - Glickman,Michael H. KW - deubiquitination KW - Proteasome KW - solenoid KW - Surface plasmon resonance (SPR) KW - ubiquitin KW - Ubiquitin-dependent protease AB - Substrates tagged with (poly)ubiquitin for degradation can be targeted directly to the 26S proteasome where they are proteolysed. Independently, ubiquitin-conjugates may also be delivered by bivalent shuttles. The majority of shuttles attach to the proteasome through a ubiquitin-like domain (UBL) while anchoring cargo at a C-terminal polyubiquitin-binding domain(s). We found that two shuttles of this class, Rad23 and Dsk2, dock at two different receptors embedded within a single subunit of the 19S proteasome regulatory particle (RP), Rpn1. Their association/dissociation constants and affinities for Rpn1 are similar. In contrast, another UBL-containing protein, the deubiquitinase Ubp6, is also anchored by Rpn1, yet dissociates slower, thus behaving as a sometimes proteasome subunit distinct from transiently-associated shuttles. Two neighboring subunits, Rpn10 and Rpn13, show a marked preference for polyubiquitin over UBLs. Rpn10 attaches to the central solenoid portion of Rpn1 although this association is stabilized by the presence of a third subunit, Rpn2. Rpn13 binds directly to the C-terminal portion of Rpn2. These intrinsic polyubiquitin receptors may compete with substrate shuttles for their polyubiquitin-conjugates, thereby aiding release of the emptied shuttles. By binding multiple ubiquitin-processing factors simultaneously, Rpn1 is uniquely suited to coordinate substrate recruitment, deubiquitination, and movement towards the catalytic core. The broad range of affinities for ubiquitin, ubiquitin-like, and non-ubiquitin signals by adjacent yet non-overlapping sites all within the Base illustrates a hub of activity that coordinates the intricate relay of substrates within the proteasome, and consequently influences substrate residency time and commitment to degradation. SN - 0021-9258, 1083-351X UR - http://www.jbc.org/content/early/2012/02/08/jbc.M111.316323 M3 - 10.1074/jbc.M111.316323 ER -