ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling

Linlin Gao, Helen Coope, Susan Grant, Ma Averil, Steven C. Ley, Edward Harhaj

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Upon virus infection, the innate immune response provides the first line of protection and rapidly induces type I interferons (IFNα/β), which mediate potent antiviral effects. To maintain homeostasis and prevent autoimmunity, IFN production is tightly regulated; however, the mechanisms of negative regulation are poorly understood. Herein, we demonstrate that the A20 binding inhibitor of NF-κB 1 (ABIN1) is a novel negative regulator of antiviral signaling. Overexpression of ABIN1 inhibited IFN-β promoter activation in response to virus infection or poly(I:C) transfection, whereas siRNA-mediated knockdown of ABIN1 enhanced IFN-β production upon virus infection. ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IκB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi. Finally, an intact ubiquitin binding domain of ABIN1 was essential for ABIN1 to interact with TBK1/IKKi and inhibit IFN-β production upon poly(I:C) transfection or virus infection. Together, these results suggest that ABIN1 requires its ubiquitin binding domain and cooperates with TAX1BP1 and A20 to restrict antiviral signaling.

Original languageEnglish (US)
Pages (from-to)36592-36602
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number42
DOIs
StatePublished - Oct 21 2011

Fingerprint

Neurofibromin 1
Virus Diseases
Viruses
Poly I-C
Antiviral Agents
Transfection
Ubiquitin
TNF Receptor-Associated Factor 3
Proteins
Interferon Type I
Ubiquitin-Protein Ligases
Autoimmunity
Innate Immunity
Small Interfering RNA
Lysine
Homeostasis
Phosphotransferases
Chemical activation
Molecules
polyriboinosinic-polyribocytidylic acid

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Gao, Linlin ; Coope, Helen ; Grant, Susan ; Averil, Ma ; Ley, Steven C. ; Harhaj, Edward. / ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 42. pp. 36592-36602.
@article{0e42f160c51641748bcb862ea9774778,
title = "ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling",
abstract = "Upon virus infection, the innate immune response provides the first line of protection and rapidly induces type I interferons (IFNα/β), which mediate potent antiviral effects. To maintain homeostasis and prevent autoimmunity, IFN production is tightly regulated; however, the mechanisms of negative regulation are poorly understood. Herein, we demonstrate that the A20 binding inhibitor of NF-κB 1 (ABIN1) is a novel negative regulator of antiviral signaling. Overexpression of ABIN1 inhibited IFN-β promoter activation in response to virus infection or poly(I:C) transfection, whereas siRNA-mediated knockdown of ABIN1 enhanced IFN-β production upon virus infection. ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IκB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi. Finally, an intact ubiquitin binding domain of ABIN1 was essential for ABIN1 to interact with TBK1/IKKi and inhibit IFN-β production upon poly(I:C) transfection or virus infection. Together, these results suggest that ABIN1 requires its ubiquitin binding domain and cooperates with TAX1BP1 and A20 to restrict antiviral signaling.",
author = "Linlin Gao and Helen Coope and Susan Grant and Ma Averil and Ley, {Steven C.} and Edward Harhaj",
year = "2011",
month = "10",
day = "21",
doi = "10.1074/jbc.M111.283762",
language = "English (US)",
volume = "286",
pages = "36592--36602",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "42",

}

ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling. / Gao, Linlin; Coope, Helen; Grant, Susan; Averil, Ma; Ley, Steven C.; Harhaj, Edward.

In: Journal of Biological Chemistry, Vol. 286, No. 42, 21.10.2011, p. 36592-36602.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling

AU - Gao, Linlin

AU - Coope, Helen

AU - Grant, Susan

AU - Averil, Ma

AU - Ley, Steven C.

AU - Harhaj, Edward

PY - 2011/10/21

Y1 - 2011/10/21

N2 - Upon virus infection, the innate immune response provides the first line of protection and rapidly induces type I interferons (IFNα/β), which mediate potent antiviral effects. To maintain homeostasis and prevent autoimmunity, IFN production is tightly regulated; however, the mechanisms of negative regulation are poorly understood. Herein, we demonstrate that the A20 binding inhibitor of NF-κB 1 (ABIN1) is a novel negative regulator of antiviral signaling. Overexpression of ABIN1 inhibited IFN-β promoter activation in response to virus infection or poly(I:C) transfection, whereas siRNA-mediated knockdown of ABIN1 enhanced IFN-β production upon virus infection. ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IκB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi. Finally, an intact ubiquitin binding domain of ABIN1 was essential for ABIN1 to interact with TBK1/IKKi and inhibit IFN-β production upon poly(I:C) transfection or virus infection. Together, these results suggest that ABIN1 requires its ubiquitin binding domain and cooperates with TAX1BP1 and A20 to restrict antiviral signaling.

AB - Upon virus infection, the innate immune response provides the first line of protection and rapidly induces type I interferons (IFNα/β), which mediate potent antiviral effects. To maintain homeostasis and prevent autoimmunity, IFN production is tightly regulated; however, the mechanisms of negative regulation are poorly understood. Herein, we demonstrate that the A20 binding inhibitor of NF-κB 1 (ABIN1) is a novel negative regulator of antiviral signaling. Overexpression of ABIN1 inhibited IFN-β promoter activation in response to virus infection or poly(I:C) transfection, whereas siRNA-mediated knockdown of ABIN1 enhanced IFN-β production upon virus infection. ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IκB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi. Finally, an intact ubiquitin binding domain of ABIN1 was essential for ABIN1 to interact with TBK1/IKKi and inhibit IFN-β production upon poly(I:C) transfection or virus infection. Together, these results suggest that ABIN1 requires its ubiquitin binding domain and cooperates with TAX1BP1 and A20 to restrict antiviral signaling.

UR - http://www.scopus.com/inward/record.url?scp=80054700914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054700914&partnerID=8YFLogxK

U2 - 10.1074/jbc.M111.283762

DO - 10.1074/jbc.M111.283762

M3 - Article

C2 - 21885437

AN - SCOPUS:80054700914

VL - 286

SP - 36592

EP - 36602

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 42

ER -