Toggle Main Menu Toggle Search

Open Access padlockePrints

The ubiquitin-associated (UBA) 1 domain of Schizosaccharomyces pombe Rhp23 is essential for the recognition of ubiquitin-proteasome system substrates both in Vitro and in Vivo

Lookup NU author(s): Professor Jane Endicott



The ubiquitin-proteasome system is essential for maintaining a functional cell. Not only does it remove incorrectly folded proteins, it also regulates protein levels to ensure their appropriate spatial and temporal distribution. Proteins marked for degradation by the addition of Lys(48)-linked ubiquitin (Ub) chains are recognized by shuttle factors and transported to the 26 S proteasome. One of these shuttle factors, Schizosaccharomyces pombe Rhp23, has an unusual domain architecture. It comprises an N-terminal ubiquitin-like domain that can recognize the proteasome followed by two ubiquitin-associated (UBA) domains, termed UBA1 and UBA2, which can bind Ub. This architecture is conserved up to humans, suggesting that both domains are important for Rhp23 function. Such an extent of conservation raises the question as to why, in contrast to all other shuttle proteins, does Rhp23 require two UBA domains? We performed in vitro Ub binding assays using domain swap chimeric proteins and mutated domains in isolation as well as in the context of the full-length protein to reveal that the Ub binding properties of the UBA domains are context-dependent. In vivo, the internal Rhp23 UBA1 domain provides sufficient Ub recognition for the protein to function without UBA2.

Publication metadata

Author(s): Medina B, Paraskevopoulos K, Boehringer J, Sznajder A, Robertson M, Endicott J, Gordon C

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2012

Volume: 287

Issue: 50

Pages: 42344-42351

Print publication date: 04/10/2012

Date deposited: 25/02/2013

ISSN (print): 0021-9258

ISSN (electronic): 1067-8816

Publisher: American Society for Biochemistry and Molecular Biology, Inc.


DOI: 10.1074/jbc.M112.419838

PubMed id: 23038266


Altmetrics provided by Altmetric