Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB+1

Michal Chojnacki; Daoning Zhang; Monika Talarowska; Piotr Gałecki; Janusz Szemraj; David Fushman; Mark A Nakasone

doi:10.1002/1873-3468.12484

Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB+1

Michal Chojnacki, Daoning Zhang, Monika Talarowska, Piotr Gałecki, Janusz Szemraj, David Fushman, Mark A Nakasone (Lead / Corresponding author)

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

The ubiquitin mutant UBB+1 has been identified as a hallmark of neurodegenerative diseases. In this study, we characterize polyubiquitinated forms of UBB+1 in vitro and from patient samples. The ability of UBB+1 to be readily ubiquitinated by several E2 enzymes provided a mechanism for the controlled synthesis and purification of defined conjugates. This allowed us to utilize polyUb-UBB+1 conjugates for biochemical assays, as well as solution NMR. Coupled with our immunoassay for detection of ubiquitinated forms of UBB+1 in patient blood samples, we gain a clearer picture of the molecular mechanisms underlying neurodegenerative diseases.

Original language	English
Pages (from-to)	4573-4585
Number of pages	13
Journal	FEBS Letters
Volume	590
Issue number	24
Early online date	22 Nov 2016
DOIs	https://doi.org/10.1002/1873-3468.12484
Publication status	Published - 23 Dec 2016

Keywords

Aged
Alzheimer Disease/genetics
Case-Control Studies
Cysteine Endopeptidases/chemistry
Deubiquitinating Enzymes
Endopeptidases/chemistry
Endosomal Sorting Complexes Required for Transport/chemistry
Female
Fluoresceins/chemistry
Fluorescent Dyes/chemistry
Gene Expression Regulation
Humans
Male
Middle Aged
Models, Molecular
Neurons/metabolism
Nuclear Magnetic Resonance, Biomolecular
Polyubiquitin/chemistry
Proteasome Endopeptidase Complex/metabolism
Protein Isoforms/chemistry
Protein Structure, Secondary
Staining and Labeling
Ubiquitin/chemistry
Ubiquitin Thiolesterase/chemistry
Ubiquitin-Specific Proteases/chemistry
Ubiquitination

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10.1002/1873-3468.12484

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title = "Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB+1",

abstract = "The ubiquitin mutant UBB+1 has been identified as a hallmark of neurodegenerative diseases. In this study, we characterize polyubiquitinated forms of UBB+1 in vitro and from patient samples. The ability of UBB+1 to be readily ubiquitinated by several E2 enzymes provided a mechanism for the controlled synthesis and purification of defined conjugates. This allowed us to utilize polyUb-UBB+1 conjugates for biochemical assays, as well as solution NMR. Coupled with our immunoassay for detection of ubiquitinated forms of UBB+1 in patient blood samples, we gain a clearer picture of the molecular mechanisms underlying neurodegenerative diseases.",

keywords = "Aged, Alzheimer Disease/genetics, Case-Control Studies, Cysteine Endopeptidases/chemistry, Deubiquitinating Enzymes, Endopeptidases/chemistry, Endosomal Sorting Complexes Required for Transport/chemistry, Female, Fluoresceins/chemistry, Fluorescent Dyes/chemistry, Gene Expression Regulation, Humans, Male, Middle Aged, Models, Molecular, Neurons/metabolism, Nuclear Magnetic Resonance, Biomolecular, Polyubiquitin/chemistry, Proteasome Endopeptidase Complex/metabolism, Protein Isoforms/chemistry, Protein Structure, Secondary, Staining and Labeling, Ubiquitin/chemistry, Ubiquitin Thiolesterase/chemistry, Ubiquitin-Specific Proteases/chemistry, Ubiquitination",

author = "Michal Chojnacki and Daoning Zhang and Monika Talarowska and Piotr Ga{\l}ecki and Janusz Szemraj and David Fushman and Nakasone, {Mark A}",

note = "NIH. Grant Number: GM065334 National Centre of Science (Poland). Grant Number: UMO-2012/05/B/NZ5/01852 NSF. Grant Number: DBI1040158 {\textcopyright} 2016 Federation of European Biochemical Societies.",

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doi = "10.1002/1873-3468.12484",

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AU - Szemraj, Janusz

AU - Fushman, David

AU - Nakasone, Mark A

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KW - Fluoresceins/chemistry

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KW - Ubiquitin Thiolesterase/chemistry

KW - Ubiquitin-Specific Proteases/chemistry

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JF - FEBS Letters

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Characterizing polyubiquitinated forms of the neurodegenerative ubiquitin mutant UBB+1

Abstract

Keywords

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