@article {18712,
	title = {Rpn1 and Rpn2 coordinate ubiquitin processing factors at the proteasome},
	journal = {Journal of Biological ChemistryJ. Biol. Chem.},
	year = {2012},
	month = {2012/02/08/},
	abstract = {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.},
	keywords = {deubiquitination, Proteasome, solenoid, Surface plasmon resonance (SPR), ubiquitin, Ubiquitin-dependent protease},
	isbn = {0021-9258, 1083-351X},
	doi = {10.1074/jbc.M111.316323},
	url = {http://www.jbc.org/content/early/2012/02/08/jbc.M111.316323},
	author = {Rosenzweig,Rina and Bronner,Vered and Zhang,Daoning and Fushman, David and Glickman,Michael H.}
}
@article {18701,
	title = {Evidence for Bidentate Substrate Binding as the Basis for the K48 Linkage Specificity of Otubain 1},
	journal = {Journal of Molecular Biology},
	volume = {386},
	year = {2009},
	month = {2009/03/06/},
	pages = {1011 - 1023},
	abstract = {Otubain 1 belongs to the ovarian tumor (OTU) domain class of cysteine protease deubiquitinating enzymes. We show here that human otubain 1 (hOtu1) is highly linkage-specific, cleaving Lys48 (K48)-linked polyubiquitin but not K63-, K29-, K6-, or K11-linked polyubiquitin, or linear α-linked polyubiquitin. Cleavage is not limited to either end of a polyubiquitin chain, and both free and substrate-linked polyubiquitin are disassembled. Intriguingly, cleavage of K48-diubiquitin by hOtu1 can be inhibited by diubiquitins of various linkage types, as well as by monoubiquitin. NMR studies and activity assays suggest that both the proximal and distal units of K48-diubiquitin bind to hOtu1. Reaction of Cys23 with ubiquitin-vinylsulfone identified a ubiquitin binding site that is distinct from the active site, which includes Cys91. Occupancy of the active site is needed to enable tight binding to the second site. We propose that distinct binding sites for the ubiquitins on either side of the scissile bond allow hOtu1 to discriminate among different isopeptide linkages in polyubiquitin substrates. Bidentate binding may be a general strategy used to achieve linkage-specific deubiquitination.},
	keywords = {deubiquitination, isopeptide, linkage specificity, otubain, polyubiquitin},
	isbn = {0022-2836},
	doi = {10.1016/j.jmb.2008.12.085},
	url = {http://www.sciencedirect.com/science/article/pii/S0022283608016124},
	author = {Wang,Tao and Yin,Luming and Cooper,Eric M. and Lai,Ming-Yih and Dickey,Seth and Pickart,Cecile M. and Fushman, David and Wilkinson,Keith D. and Cohen,Robert E. and Wolberger,Cynthia}
}
