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Book ; Online: Modulating Cytokines as Treatment for Autoimmune Diseases and Cancer

Mortier, Erwan / Ma, Averil / Malynn, Barbara A. / Neurath, Markus

2020

Keywords	Medicine ; Immunology ; cytokine ; oncology ; inflammation ; inhibitor ; therapy
Size	1 electronic resource (202 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021230441
ISBN	9782889662111 ; 288966211X
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: A20: A multifunctional tool for regulating immunity and preventing disease.

Malynn, Barbara A / Ma, Averil

Cellular immunology

2019 Volume 340, Page(s) 103914

Abstract: A20, also known as TNFAIP3, is a potent regulator of ubiquitin (Ub) dependent signals. A20 prevents multiple human diseases, indicating that the critical functions of this protein are clinically as well as biologically impactful. As revealed by mouse ... ...

Abstract	A20, also known as TNFAIP3, is a potent regulator of ubiquitin (Ub) dependent signals. A20 prevents multiple human diseases, indicating that the critical functions of this protein are clinically as well as biologically impactful. As revealed by mouse models, cell specific functions of A20 are linked to its ability to regulate diverse signaling pathways. Aberrant expression or functions of A20 in specific cell types underlie divergent disease outcomes. Discernment of A20's biochemical functions and their phenotypic outcomes will contribute to our understanding of how ubiquitination is regulated, how Ub mediated functions can prevent disease, and will pave the way for future therapeutic interventions.
MeSH term(s)	Animals ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/pathology ; Arthritis, Rheumatoid/prevention & control ; Asthma/genetics ; Asthma/immunology ; Asthma/pathology ; Asthma/prevention & control ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; Disease Models, Animal ; Humans ; Immunity, Innate/drug effects ; Immunologic Factors/therapeutic use ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/pathology ; Lupus Erythematosus, Systemic/prevention & control ; Molecular Targeted Therapy/methods ; NF-kappa B/genetics ; NF-kappa B/immunology ; Protein Processing, Post-Translational ; Signal Transduction ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; Tumor Necrosis Factor alpha-Induced Protein 3/genetics ; Tumor Necrosis Factor alpha-Induced Protein 3/immunology ; Ubiquitination
Chemical Substances	Immunologic Factors ; NF-kappa B ; TNFAIP3 protein, human (EC 3.4.19.12) ; Tumor Necrosis Factor alpha-Induced Protein 3 (EC 3.4.19.12)
Language	English
Publishing date	2019-04-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	80094-6
ISSN	1090-2163 ; 0008-8749
ISSN (online)	1090-2163
ISSN	0008-8749
DOI	10.1016/j.cellimm.2019.04.002
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Article ; Online: Preserving immune homeostasis with A20.

Razani, Bahram / Malynn, Barbara A / Ma, Averil

Advances in immunology

2020 Volume 148, Page(s) 1–48

Abstract: A20/TNFAIP3 is a TNF induced gene that plays a profound role in preserving cellular and organismal homeostasis (Lee, et al., 2000; Opipari etal., 1990). This protein has been linked to multiple human diseases via genetic, epigenetic, and an emerging ... ...

Abstract	A20/TNFAIP3 is a TNF induced gene that plays a profound role in preserving cellular and organismal homeostasis (Lee, et al., 2000; Opipari etal., 1990). This protein has been linked to multiple human diseases via genetic, epigenetic, and an emerging series of patients with mono-allelic coding mutations. Diverse cellular functions of this pleiotropically expressed protein include immune-suppressive, anti-inflammatory, and cell protective functions. The A20 protein regulates ubiquitin dependent cell signals; however, the biochemical mechanisms by which it performs these functions is surprisingly complex. Deciphering these cellular and biochemical facets of A20 dependent biology should greatly improve our understanding of murine and human disease pathophysiology as well as unveil new mechanisms of cell and tissue biology.
MeSH term(s)	Animals ; Autoimmunity ; Cell Death ; Homeostasis ; Humans ; Inflammation/immunology ; Mice ; Mutation/genetics ; Tumor Necrosis Factor alpha-Induced Protein 3/metabolism
Chemical Substances	TNFAIP3 protein, human (EC 3.4.19.12) ; Tumor Necrosis Factor alpha-Induced Protein 3 (EC 3.4.19.12)
Language	English
Publishing date	2020-10-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	80226-8
ISSN	1557-8445 ; 0065-2776
ISSN (online)	1557-8445
ISSN	0065-2776
DOI	10.1016/bs.ai.2020.10.001
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Article ; Online: Editorial: Modulating Cytokines as Treatment for Autoimmune Diseases and Cancer.

Mortier, Erwan / Ma, Averil / Malynn, Barbara A / Neurath, Markus F

Frontiers in immunology

2020 Volume 11, Page(s) 608636

MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; Cytokines/immunology ; Humans ; Inflammation/immunology ; Neoplasms/immunology
Chemical Substances	Cytokines
Language	English
Publishing date	2020-10-15
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.608636
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome.

Kattah, Michael G / Malynn, Barbara A / Ma, Averil

Journal of molecular biology

2017 Volume 429, Issue 22, Page(s) 3471–3485

Abstract: Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety of intracellular signaling pathways. Inflammatory signaling cascades downstream of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all rely on ... ...

Abstract	Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety of intracellular signaling pathways. Inflammatory signaling cascades downstream of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all rely on ubiquitination events to direct subsequent immune responses. In the past several years, inflammasome activation and subsequent signal transduction have emerged as an excellent example of how ubiquitin signals control inflammatory responses. Inflammasomes are multiprotein signaling complexes that ultimately lead to caspase activation and release of the interleukin-1 (IL-1) family members, IL-1β and IL-18. Inflammasome activation is critical for the host's defense against pathogens, but dysregulation of inflammasomes may contribute to the pathogenesis of multiple diseases. Ultimately, understanding how various ubiquitin interacting proteins control inflammatory signaling cascades could provide new pathways for therapeutic intervention. Here we review specific ubiquitin-modifying enzymes and ubiquitination events that orchestrate inflammatory responses, with an emphasis on the NLRP3 inflammasome.
MeSH term(s)	Animals ; Deubiquitinating Enzymes/metabolism ; Humans ; Inflammasomes/metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligase Complexes/metabolism
Chemical Substances	Inflammasomes ; Ubiquitin ; Ubiquitin-Protein Ligase Complexes (EC 2.3.2.23) ; Deubiquitinating Enzymes (EC 3.4.19.12)
Language	English
Publishing date	2017-10-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2017.10.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A20: linking a complex regulator of ubiquitylation to immunity and human disease.

Ma, Averil / Malynn, Barbara A

Nature reviews. Immunology

2012 Volume 12, Issue 11, Page(s) 774–785

Abstract: A20 (also known as TNFAIP3) is a potent anti-inflammatory signalling molecule that restricts multiple intracellular signalling cascades. Recent studies in three general areas have converged to highlight the clinical and biological importance of A20. ... ...

Abstract	A20 (also known as TNFAIP3) is a potent anti-inflammatory signalling molecule that restricts multiple intracellular signalling cascades. Recent studies in three general areas have converged to highlight the clinical and biological importance of A20. First, human genetic studies have strongly linked polymorphisms and mutations in the gene encoding A20 to inflammatory, autoimmune and malignant diseases. Second, studies in gene-targeted mice have revealed that A20 regulates multiple immune cell functions and prevents experimental diseases that closely mimic human conditions. Third, biochemical studies have unveiled complex mechanisms by which A20 regulates ubiquitin-dependent nuclear factor-κB and cell-survival signals. Taken together, these studies are revealing the importance of A20-mediated regulation of ubiquitin-dependent signalling in human disease.
MeSH term(s)	Animals ; Autoimmune Diseases/genetics ; Autoimmune Diseases/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation Mediators ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; NF-kappa B/immunology ; NF-kappa B/metabolism ; Neoplasms/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Signal Transduction ; Tumor Necrosis Factor alpha-Induced Protein 3 ; Ubiquitination
Chemical Substances	DNA-Binding Proteins ; Inflammation Mediators ; Intracellular Signaling Peptides and Proteins ; NF-kappa B ; Nuclear Proteins ; TNFAIP3 protein, human (EC 3.4.19.12) ; Tumor Necrosis Factor alpha-Induced Protein 3 (EC 3.4.19.12)
Language	English
Publishing date	2012-10-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/nri3313
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Article ; Online: OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination.

Pasupala, Nagesh / Morrow, Marie E / Que, Lauren T / Malynn, Barbara A / Ma, Averil / Wolberger, Cynthia

The Journal of biological chemistry

2018 Volume 293, Issue 47, Page(s) 18285–18295

Abstract: OTUB1 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains and also regulates ubiquitin signaling through a unique, noncatalytic mechanism. OTUB1 binds to a subset of E2 ubiquitin-conjugating enzymes and inhibits their activity by ...

Abstract	OTUB1 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains and also regulates ubiquitin signaling through a unique, noncatalytic mechanism. OTUB1 binds to a subset of E2 ubiquitin-conjugating enzymes and inhibits their activity by trapping the E2∼ubiquitin thioester and preventing ubiquitin transfer. The same set of E2s stimulate the deubiquitinating activity of OTUB1 when the E2 is not charged with ubiquitin. Previous studies have shown that, in cells, OTUB1 binds to E2-conjugating enzymes of the UBE2D (UBCH5) and UBE2E families, as well as to UBE2N (UBC13). Cellular roles have been identified for the interaction of OTUB1 with UBE2N and members of the UBE2D family, but not for interactions with UBE2E E2 enzymes. We report here a novel role for OTUB1-E2 interactions in modulating E2 protein ubiquitination. We observe that
MeSH term(s)	Amino Acid Motifs ; Animals ; Cysteine Endopeptidases/genetics ; Cysteine Endopeptidases/metabolism ; Mice ; Mice, Inbred C57BL ; Protein Binding ; Protein Stability ; Ubiquitin/metabolism ; Ubiquitin-Conjugating Enzymes/chemistry ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitination
Chemical Substances	Ubiquitin ; UBE2E1 protein, human (EC 2.3.2.23) ; Ube2e1 protein, mouse (EC 2.3.2.23) ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Cysteine Endopeptidases (EC 3.4.22.-) ; OTUB1 protein, human (EC 3.4.22.-) ; Otub1 protein, mouse (EC 3.4.22.-)
Language	English
Publishing date	2018-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA118.004677
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ubiquitin makes its mark on immune regulation.

Malynn, Barbara A / Ma, Averil

Immunity

2010 Volume 33, Issue 6, Page(s) 843–852

Abstract: Ubiquitination, the covalent attachment of ubiquitin molecules to proteins, is emerging as a widely utilized mechanism for rapidly regulating cell signaling. Recent studies indicate that ubiquitination plays potent roles in regulating a variety of ... ...

Abstract	Ubiquitination, the covalent attachment of ubiquitin molecules to proteins, is emerging as a widely utilized mechanism for rapidly regulating cell signaling. Recent studies indicate that ubiquitination plays potent roles in regulating a variety of signals in both innate and adaptive immune cells. Here, we will review recent studies of ubiquitin ligases, ubiquitin chain linkages, and ubiquitin binding proteins that highlight the diversity and specificity of ubiquitin dependent functions in immune cells. We will also review studies that shed light on how ubiquitination signals are integrated in cell-type-specific fashion to regulate the immune system in vivo.
MeSH term(s)	Adaptive Immunity ; Animals ; Humans ; Immunity, Innate ; Immunomodulation ; Mice ; NF-kappa B/immunology ; Signal Transduction/immunology ; Ubiquitin/immunology ; Ubiquitin-Conjugating Enzymes/immunology
Chemical Substances	NF-kappa B ; Ubiquitin ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23)
Language	English
Publishing date	2010-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2010.12.007
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Article: Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome

Kattah, Michael G / Averil Ma / Barbara A. Malynn

Journal of Molecular Biology. 2017,

2017

Abstract	Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety of intracellular signaling pathways. Inflammatory signaling cascades downstream of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all rely on ubiquitination events to direct subsequent immune responses. In the past several years, inflammasome activation and subsequent signal transduction have emerged as an excellent example of how ubiquitin signals control inflammatory responses. Inflammasomes are multiprotein signaling complexes that ultimately lead to caspase activation and release of the interleukin-1 (IL-1) family members, IL-1Î² and IL-18. Inflammasome activation is critical for the host's defense against pathogens, but dysregulation of inflammasomes may contribute to the pathogenesis of multiple diseases. Ultimately, understanding how various ubiquitin interacting proteins control inflammatory signaling cascades could provide new pathways for therapeutic intervention. Here we review specific ubiquitin-modifying enzymes and ubiquitination events that orchestrate inflammatory responses, with an emphasis on the NLRP3 inflammasome.
Keywords	agonists ; antigens ; caspases ; crosslinking ; cytokine receptors ; immune response ; inflammasomes ; inflammation ; interleukin-18 ; interleukin-1beta ; pathogenesis ; pathogens ; signal transduction ; tumor necrosis factors ; ubiquitin ; ubiquitination
Language	English
Size	p. .
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2017.10.001
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A20 takes on tumors: tumor suppression by an ubiquitin-editing enzyme.

Malynn, Barbara A / Ma, Averil

The Journal of experimental medicine

2009 Volume 206, Issue 5, Page(s) 977–980

Abstract: Many B cell cancers are characterized in part by the dysregulation of the NF-kappaB signaling pathway. A new study identifies somatic mutations in TNFAIP3, the gene encoding the NF-kappaB inhibitor A20, in Hodgkin lymphomas and primary mediastinal ... ...

Abstract	Many B cell cancers are characterized in part by the dysregulation of the NF-kappaB signaling pathway. A new study identifies somatic mutations in TNFAIP3, the gene encoding the NF-kappaB inhibitor A20, in Hodgkin lymphomas and primary mediastinal lymphomas. These data reveal the role of A20 as a tumor suppressor protein.
MeSH term(s)	Animals ; Autoimmunity ; B-Lymphocytes/immunology ; DNA-Binding Proteins ; Female ; Hodgkin Disease/genetics ; Humans ; Immunity, Innate ; Intracellular Signaling Peptides and Proteins/deficiency ; Intracellular Signaling Peptides and Proteins/genetics ; Lymphocytes/immunology ; Lymphoma/genetics ; Lymphoma, B-Cell/genetics ; Lymphoma, B-Cell/immunology ; Mice ; Mice, Knockout ; Mutation ; NF-kappa B/physiology ; Neoplasms/genetics ; Nuclear Proteins/deficiency ; Nuclear Proteins/genetics ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/immunology ; Tumor Necrosis Factor alpha-Induced Protein 3 ; Tumor Necrosis Factor-alpha/genetics ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	DNA-Binding Proteins ; Intracellular Signaling Peptides and Proteins ; NF-kappa B ; Nuclear Proteins ; Tumor Necrosis Factor-alpha ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; TNFAIP3 protein, human (EC 3.4.19.12) ; Tumor Necrosis Factor alpha-Induced Protein 3 (EC 3.4.19.12)
Language	English
Publishing date	2009-04-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20090765
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