SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling

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SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling. / Elliott, Paul R; Leske, Derek; Hrdinka, Matous; Bagola, Katrin; Fiil, Berthe K; McLaughlin, Stephen H; Wagstaff, Jane; Volkmar, Norbert; Christianson, John C; Kessler, Benedikt M; Freund, Stefan M V; Komander, David; Gyrd-Hansen, Mads.

In: Molecular Cell, Vol. 63, No. 6, 15.09.2016, p. 990-1005.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Elliott, PR, Leske, D, Hrdinka, M, Bagola, K, Fiil, BK, McLaughlin, SH, Wagstaff, J, Volkmar, N, Christianson, JC, Kessler, BM, Freund, SMV, Komander, D & Gyrd-Hansen, M 2016, 'SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling', Molecular Cell, vol. 63, no. 6, pp. 990-1005. https://doi.org/10.1016/j.molcel.2016.08.001

APA

Elliott, P. R., Leske, D., Hrdinka, M., Bagola, K., Fiil, B. K., McLaughlin, S. H., Wagstaff, J., Volkmar, N., Christianson, J. C., Kessler, B. M., Freund, S. M. V., Komander, D., & Gyrd-Hansen, M. (2016). SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling. Molecular Cell, 63(6), 990-1005. https://doi.org/10.1016/j.molcel.2016.08.001

Vancouver

Elliott PR, Leske D, Hrdinka M, Bagola K, Fiil BK, McLaughlin SH et al. SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling. Molecular Cell. 2016 Sep 15;63(6):990-1005. https://doi.org/10.1016/j.molcel.2016.08.001

Author

Elliott, Paul R ; Leske, Derek ; Hrdinka, Matous ; Bagola, Katrin ; Fiil, Berthe K ; McLaughlin, Stephen H ; Wagstaff, Jane ; Volkmar, Norbert ; Christianson, John C ; Kessler, Benedikt M ; Freund, Stefan M V ; Komander, David ; Gyrd-Hansen, Mads. / SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling. In: Molecular Cell. 2016 ; Vol. 63, No. 6. pp. 990-1005.

Bibtex

@article{ca36176ea2894042aa96faec83317407,
title = "SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling",
abstract = "The linear ubiquitin chain assembly complex (LUBAC) regulates immune signaling, and its function is regulated by the deubiquitinases OTULIN and CYLD, which associate with the catalytic subunit HOIP. However, the mechanism through which CYLD interacts with HOIP is unclear. We here show that CYLD interacts with HOIP via spermatogenesis-associated protein 2 (SPATA2). SPATA2 interacts with CYLD through its non-canonical PUB domain, which binds the catalytic CYLD USP domain in a CYLD B-box-dependent manner. Significantly, SPATA2 binding activates CYLD-mediated hydrolysis of ubiquitin chains. SPATA2 also harbors a conserved PUB-interacting motif that selectively docks into the HOIP PUB domain. In cells, SPATA2 is recruited to the TNF receptor 1 signaling complex and is required for CYLD recruitment. Loss of SPATA2 increases ubiquitination of LUBAC substrates and results in enhanced NOD2 signaling. Our data reveal SPATA2 as a high-affinity binding partner of CYLD and HOIP, and a regulatory component of LUBAC-mediated NF-κB signaling.",
keywords = "Amino Acid Sequence, Binding Sites, Cloning, Molecular, Crystallography, X-Ray, Deubiquitinating Enzyme CYLD, Endopeptidases/chemistry, Escherichia coli/genetics, Gene Expression, Gene Expression Regulation, Humans, Immunity, Innate, Kinetics, Molecular Docking Simulation, NF-kappa B/chemistry, Nod2 Signaling Adaptor Protein/chemistry, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Proteins/chemistry, Recombinant Proteins/chemistry, Sequence Alignment, Sequence Homology, Amino Acid, Signal Transduction, Substrate Specificity, Tumor Suppressor Proteins/chemistry, Ubiquitin/chemistry, Ubiquitin-Protein Ligases/chemistry",
author = "Elliott, {Paul R} and Derek Leske and Matous Hrdinka and Katrin Bagola and Fiil, {Berthe K} and McLaughlin, {Stephen H} and Jane Wagstaff and Norbert Volkmar and Christianson, {John C} and Kessler, {Benedikt M} and Freund, {Stefan M V} and David Komander and Mads Gyrd-Hansen",
note = "Copyright {\textcopyright} 2016 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = sep,
day = "15",
doi = "10.1016/j.molcel.2016.08.001",
language = "English",
volume = "63",
pages = "990--1005",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - SPATA2 Links CYLD to LUBAC, Activates CYLD, and Controls LUBAC Signaling

AU - Elliott, Paul R

AU - Leske, Derek

AU - Hrdinka, Matous

AU - Bagola, Katrin

AU - Fiil, Berthe K

AU - McLaughlin, Stephen H

AU - Wagstaff, Jane

AU - Volkmar, Norbert

AU - Christianson, John C

AU - Kessler, Benedikt M

AU - Freund, Stefan M V

AU - Komander, David

AU - Gyrd-Hansen, Mads

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/9/15

Y1 - 2016/9/15

N2 - The linear ubiquitin chain assembly complex (LUBAC) regulates immune signaling, and its function is regulated by the deubiquitinases OTULIN and CYLD, which associate with the catalytic subunit HOIP. However, the mechanism through which CYLD interacts with HOIP is unclear. We here show that CYLD interacts with HOIP via spermatogenesis-associated protein 2 (SPATA2). SPATA2 interacts with CYLD through its non-canonical PUB domain, which binds the catalytic CYLD USP domain in a CYLD B-box-dependent manner. Significantly, SPATA2 binding activates CYLD-mediated hydrolysis of ubiquitin chains. SPATA2 also harbors a conserved PUB-interacting motif that selectively docks into the HOIP PUB domain. In cells, SPATA2 is recruited to the TNF receptor 1 signaling complex and is required for CYLD recruitment. Loss of SPATA2 increases ubiquitination of LUBAC substrates and results in enhanced NOD2 signaling. Our data reveal SPATA2 as a high-affinity binding partner of CYLD and HOIP, and a regulatory component of LUBAC-mediated NF-κB signaling.

AB - The linear ubiquitin chain assembly complex (LUBAC) regulates immune signaling, and its function is regulated by the deubiquitinases OTULIN and CYLD, which associate with the catalytic subunit HOIP. However, the mechanism through which CYLD interacts with HOIP is unclear. We here show that CYLD interacts with HOIP via spermatogenesis-associated protein 2 (SPATA2). SPATA2 interacts with CYLD through its non-canonical PUB domain, which binds the catalytic CYLD USP domain in a CYLD B-box-dependent manner. Significantly, SPATA2 binding activates CYLD-mediated hydrolysis of ubiquitin chains. SPATA2 also harbors a conserved PUB-interacting motif that selectively docks into the HOIP PUB domain. In cells, SPATA2 is recruited to the TNF receptor 1 signaling complex and is required for CYLD recruitment. Loss of SPATA2 increases ubiquitination of LUBAC substrates and results in enhanced NOD2 signaling. Our data reveal SPATA2 as a high-affinity binding partner of CYLD and HOIP, and a regulatory component of LUBAC-mediated NF-κB signaling.

KW - Amino Acid Sequence

KW - Binding Sites

KW - Cloning, Molecular

KW - Crystallography, X-Ray

KW - Deubiquitinating Enzyme CYLD

KW - Endopeptidases/chemistry

KW - Escherichia coli/genetics

KW - Gene Expression

KW - Gene Expression Regulation

KW - Humans

KW - Immunity, Innate

KW - Kinetics

KW - Molecular Docking Simulation

KW - NF-kappa B/chemistry

KW - Nod2 Signaling Adaptor Protein/chemistry

KW - Protein Binding

KW - Protein Interaction Domains and Motifs

KW - Protein Structure, Secondary

KW - Proteins/chemistry

KW - Recombinant Proteins/chemistry

KW - Sequence Alignment

KW - Sequence Homology, Amino Acid

KW - Signal Transduction

KW - Substrate Specificity

KW - Tumor Suppressor Proteins/chemistry

KW - Ubiquitin/chemistry

KW - Ubiquitin-Protein Ligases/chemistry

U2 - 10.1016/j.molcel.2016.08.001

DO - 10.1016/j.molcel.2016.08.001

M3 - Journal article

C2 - 27591049

VL - 63

SP - 990

EP - 1005

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 6

ER -

ID: 280717896