JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome

Ambroggio, Xavier; Rees, Douglas C.; Deshaies, Raymond J.

doi:10.1371/journal.pbio.0020002

Cited by 212 publications

(223 citation statements)

References 37 publications

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“…Indeed, there may be a difference among DUBs in terms of their mode of action: one group may function by direct recognition of their substrates, while the other group, including the JAMM domain-containing isopeptidases, may function as a constituent of a complex (Amerik and Hochstrasser, 2004). The unique structures of the catalytic regions of the DUBs, as well as the presence of specific sets of interaction domains in the different DUBs may explain such differences (Ambroggio et al, 2004). Interestingly, unlike the ESCRT-0, -I, and -II components, ESCRT-III constituents seem to lack previously identified ubiquitin-binding motifs.…”

Section: Discussionmentioning

confidence: 99%

“…For comparison, we prepared an enzymatically inactive AMSH, AMSH E280A , basing our construct design on a report in which replacement of a glutamic acid residue (E20) by alanine within the JAMM motif of the Archaeoglobus fulgidus AfJAMM protein completely abolished the catalytic activity (Ambroggio et al, 2004). To verify that the AMSH E280A mutant possessed no DUB activity, we performed an in vitro deubiquitination assay.…”

Section: Amsh Associates With the Escrt-iii Protein Chmp3mentioning

confidence: 99%

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AMSH, an ESCRT-III Associated Enzyme, Deubiquitinates Cargo on MVB/Late Endosomes

Kyuuma

Kikuchi

Kojima

et al. 2006

Cell Struct. Funct.

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and 6 These two authors contributed equally to this work.ABSTRACT. The appropriate sorting of vesicular cargo, including cell-surface proteins, is critical for many cellular functions. Ubiquitinated cargo is targeted to endosomes and digested by lysosomal enzymes. We previously identified AMSH, a deubiquitination enzyme (DUB), to be involved in vesicular transport. Here, we purified an AMSH-binding protein, CHMP3, which is an ESCRT-III subunit. ESCRT-III functions on maturing endosomes, indicating AMSH might also play a role in MVB/late endosomes. Expression of an AMSH mutant lacking CHMP3-binding ability resulted in aberrant endosomes with accumulations of ubiquitinated cargo. Nevertheless, CHMP3-binding capability was not essential for AMSH's in vitro DUB activity or its endosomal localization, suggesting that, in vivo, the deubiquitination of endosomal cargo is CHMP3-dependent. Ubiquitinated cargo also accumulated on endosomes when catalytically inactive AMSH was expressed or AMSH was depleted. These results suggest that both the DUB activity of AMSH and its CHMP3-binding ability are required to clear ubiquitinated cargo from endosomes.

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Section: Discussionmentioning

confidence: 99%

Section: Amsh Associates With the Escrt-iii Protein Chmp3mentioning

confidence: 99%

AMSH, an ESCRT-III Associated Enzyme, Deubiquitinates Cargo on MVB/Late Endosomes

Kyuuma

Kikuchi

Kojima

et al. 2006

Cell Struct. Funct.

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“…JAMMs contain a signature 'H-x-H-P-x[6]-S-x[2]-D' motif within the MPN domain that, through its invariant His and Asp residues, coordinates a zinc atom, which is required for activity (12,47,56,169,170,225,284). JAMMs are generally incorporated into large multimeric complexes such as the proteasome lid complex (POH1/Rpn11), COP9 signalosome (CSN5), and the endocytic ESCRT machinery (AMSH) (39,46,72).…”

Section: E Jamm Familymentioning

confidence: 99%

Deubiquitylases From Genes to Organism

Clague

Barsukov

Coulson

et al. 2013

Physiological Reviews

376

384

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Ubiquitylation is a major posttranslational modification that controls most complex aspects of cell physiology. It is reversed through the action of a large family of deubiquitylating enzymes (DUBs) that are emerging as attractive therapeutic targets for a number of disease conditions. Here, we provide a comprehensive analysis of the complement of human DUBs, indicating structural motifs, typical cellular copy numbers, and tissue expression profiles. We discuss the means by which specificity is achieved and how DUB activity may be regulated. Generically DUB catalytic activity may be used to 1) maintain free ubiquitin levels, 2) rescue proteins from ubiquitin-mediated degradation, and 3) control the dynamics of ubiquitin-mediated signaling events. Functional roles of individual DUBs from each of five subfamilies in specific cellular processes are highlighted with an emphasis on those linked to pathological conditions where the association is supported by whole organism models. We then specifically consider the role of DUBs associated with protein degradative machineries and the influence of specific DUBs upon expression of receptors and channels at the plasma membrane.

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“…Nevertheless, CSN5 or RPN11 protein alone are inactive in the absence of association with CSN or the proteasome, respectively. Recently, the crystal structure of an Archaeoglobus fulgidus JAMM domain-containing protein (AF2198) has been determined, which confirmed that a zinc ion was present in the catalytic center (Tran et al, 2003;Ambroggio et al, 2004). However, the CSN5-dependent metalloprotease activity is not essential in fission yeast, where no obvious phenotype has been detected in the csn5 mutant Mundt et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The Arabidopsis CSN5A and CSN5B Subunits Are Present in Distinct COP9 Signalosome Complexes, and Mutations in Their JAMM Domains Exhibit Differential Dominant Negative Effects on Development

2004

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The COP9 signalosome (CSN) is an evolutionarily conserved multisubunit protein complex involved in a variety of signaling and developmental processes through the regulation of protein ubiquitination and degradation. A known biochemical role attributed to CSN is a metalloprotease activity responsible for the derubylation of cullins, core components for several types of ubiquitin E3 ligases. The CSN's derubylation catalytic center resides in its subunit 5, which in Arabidopsis thaliana is encoded by two homologous genes, CSN5A and CSN5B. Here, we show that CSN5A and CSN5B subunits are assembled into distinct CSN complexes in vivo, which are present in drastically different abundances, with CSN CSN5A appearing to be the dominant one. Transgenic CSN5A and CSN5B proteins carrying a collection of single mutations in or surrounding the metalloprotease catalytic center are properly assembled into CSN complexes, but only mutations in CSN5A result in a pleiotropic dominant negative phenotype. The extent of phenotypic effects caused by mutations in CSN5A is reflected at the molecular level by impairment in Cullin1 derubylation. These results reveal that three key metal binding residues as well as two other amino acids outside the catalytic center play important roles in CSN derubylation activity. Taken together, our data provide physiological evidence on a positive role of CSN in the regulation of Arabidopsis SCF (for Skp1-Cullin-F-box) E3 ligases through RUB (for Related to Ubiquitin) deconjugation and highlight the unequal role that CSN CSN5A and CSN CSN5B play in controlling the cellular derubylation of cullins. The initial characterization of CSN5A and CSN5B insertion mutants further supports these findings and provides genetic evidence on their unequal role in plant development.

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JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome

Cited by 212 publications

References 37 publications

AMSH, an ESCRT-III Associated Enzyme, Deubiquitinates Cargo on MVB/Late Endosomes

AMSH, an ESCRT-III Associated Enzyme, Deubiquitinates Cargo on MVB/Late Endosomes

Deubiquitylases From Genes to Organism

The Arabidopsis CSN5A and CSN5B Subunits Are Present in Distinct COP9 Signalosome Complexes, and Mutations in Their JAMM Domains Exhibit Differential Dominant Negative Effects on Development

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