TAX1BP1 restrains virus-induced apoptosis by facilitating itch-mediated degradation of the mitochondrial adaptor MAVS

Young Bong Choi, Noula Shembade, Kislay Parvatiyar, Siddharth Balachandran, Edward Harhaj

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The host response to RNA virus infection consists of an intrinsic innate immune response and the induction of apoptosis as mechanisms to restrict viral replication. The mitochondrial adaptor molecule MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; however, the regulation of MAVS-mediated apoptosis is poorly understood. Here, we show that the adaptor protein TAX1BP1 functions as a negative regulator of virus-induced apoptosis. TAX1BP1-deficient cells are highly sensitive to apoptosis in response to infection with the RNA viruses vesicular stomatitis virus and Sendai virus and to transfection with poly(I·C). TAX1BP1 undergoes degradation during RNA virus infection, and loss of TAX1BP1 is associated with apoptotic cell death. TAX1BP1 deficiency augments virus-induced activation of proapoptotic c-Jun N-terminal kinase (JNK) signaling. Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS. TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression. Together, these results indicate that TAX1BP1 functions as an adaptor molecule for Itch to target MAVS during RNA virus infection and thus restrict virus-induced apoptosis.

Original languageEnglish (US)
Article numbere00422-16
JournalMolecular and cellular biology
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2017

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RNA Virus Infections
Apoptosis
Viruses
Sendai virus
Virus Activation
Interferon Type I
Vesicular Stomatitis
Ubiquitin-Protein Ligases
JNK Mitogen-Activated Protein Kinases
Ubiquitination
Virus Diseases
Innate Immunity
Transfection
Proteins
Cell Death

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Choi, Young Bong ; Shembade, Noula ; Parvatiyar, Kislay ; Balachandran, Siddharth ; Harhaj, Edward. / TAX1BP1 restrains virus-induced apoptosis by facilitating itch-mediated degradation of the mitochondrial adaptor MAVS. In: Molecular and cellular biology. 2017 ; Vol. 37, No. 1.
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TAX1BP1 restrains virus-induced apoptosis by facilitating itch-mediated degradation of the mitochondrial adaptor MAVS. / Choi, Young Bong; Shembade, Noula; Parvatiyar, Kislay; Balachandran, Siddharth; Harhaj, Edward.

In: Molecular and cellular biology, Vol. 37, No. 1, e00422-16, 01.01.2017.

Research output: Contribution to journalArticle

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