Noa Reis

Bio: Noa Reis is an academic researcher from Technion – Israel Institute of Technology. The author has contributed to research in topics: Proteasome & Ubiquitin. The author has an hindex of 13, co-authored 16 publications receiving 1072 citations.

Subunit interaction maps for the regulatory particle of the 26S proteasome and the COP9 signalosome

Abstract: The 26S proteasome plays a major role in eukaryotic protein breakdown, especially for ubiquitin-tagged proteins Substrate specificity is conferred by the regulatory particle (RP), which can dissociate into stable lid and base subcomplexes To help define the molecular organization of the RP, we tested all possible paired interactions among subunits from Saccharomyces cerevisiae by yeast two-hybrid analysis Within the base, a Rpt4/5/3/6 interaction cluster was evident Within the lid, a structural cluster formed around Rpn5/11/9/8 Interactions were detected among synonymous subunits (Csn4/5/7/6) from the evolutionarily related COP9 signalosome (CSN) from Arabidopsis, implying a similar quaternary arrangement No paired interactions were detected between lid, base or core particle subcomplexes, suggesting that stable contacts between them require prior assembly Mutational analysis defined the ATPase, coiled-coil, PCI and MPN domains as important for RP assembly A single residue in the vWA domain of Rpn10 is essential for amino acid analog resistance, for degrading a ubiquitin fusion degradation substrate and for stabilizing lid–base association Comprehensive subunit interaction maps for the 26S proteasome and CSN support the ancestral relationship of these two complexes

MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function

Abstract: Background Three macromolecular assemblages, the lid complex of the proteasome, the COP9-Signalosome (CSN) and the eIF3 complex, all consist of multiple proteins harboring MPN and PCI domains. Up to now, no specific function for any of these proteins has been defined, nor has the importance of these motifs been elucidated. In particular Rpn11, a lid subunit, serves as the paradigm for MPN-containing proteins as it is highly conserved and important for proteasome function.

The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction

Abstract: Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, conside...

Breaking the chains: structure and function of the deubiquitinases.

Abstract: Ubiquitylation is a reversible protein modification that is implicated in many cellular functions. Recently, much progress has been made in the characterization of a superfamily of isopeptidases that remove ubiquitin: the deubiquitinases (DUBs; also known as deubiquitylating or deubiquitinating enzymes). Far from being uniform in structure and function, these enzymes display a myriad of distinct mechanistic features. The small number (<100) of DUBs might at first suggest a low degree of selectivity; however, DUBs are subject to multiple layers of regulation that modulate both their activity and their specificity. Due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets.

Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome

Abstract: The proteasome is an intricate molecular machine, which serves to degrade proteins following their conjugation to ubiquitin. Substrates dock onto the proteasome at its 19-subunit regulatory particle via a diverse set of ubiquitin receptors and are then translocated into an internal chamber within the 28-subunit proteolytic core particle (CP), where they are hydrolyzed. Substrate is threaded into the CP through a narrow gated channel, and thus translocation requires unfolding of the substrate. Six distinct ATPases in the regulatory particle appear to form a ring complex and to drive unfolding as well as translocation. ATP-dependent, degradation-coupled deubiquitination of the substrate is required both for efficient substrate degradation and for preventing the degradation of the ubiquitin tag. However, the proteasome also contains deubiquitinating enzymes (DUBs) that can remove ubiquitin before substrate degradation initiates, thus allowing some substrates to dissociate from the proteasome and escape degradation. Here we examine the key elements of this molecular machine and how they cooperate in the processing of proteolytic substrates.

The ubiquitin 26S proteasome proteolytic pathway

Abstract: Much of plant physiology, growth, and development is controlled by the selective removal of short-lived regulatory proteins. One important proteolytic pathway involves the small protein ubiquitin (Ub) and the 26S proteasome, a 2-MDa protease complex. In this pathway, Ub is attached to proteins destined for degradation; the resulting Ub-protein conjugates are then recognized and catabolized by the 26S proteasome. This review describes our current understanding of the pathway in plants at the biochemical, genomic, and genetic levels, using Arabidopsis thaliana as the model. Collectively, these analyses show that the Ub/26S proteasome pathway is one of the most elaborate regulatory mechanisms in plants. The genome of Arabidopsis encodes more than 1400 (or >5% of the proteome) pathway components that can be connected to almost all aspects of its biology. Most pathway components participate in the Ub-ligation reactions that choose with exquisite specificity which proteins should be ubiquitinated. What remains to be determined is the identity of the targets, which may number in the thousands in plants.