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Rhesus monkey TRIM5α protein SPRY domain contributes to AP-1 activation

Lei Na1, Yan-Dong Tang1, Cuihui Wang1

  • 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China.

The Journal of Biological Chemistry
|December 3, 2017
PubMed

Insights

The TRIM5α protein

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • TRIM5α is a key host restriction factor that inhibits retroviral infections.
  • It recognizes and binds retroviral capsids, mediating post-entry restriction.
  • Human TRIM5α also acts as an innate immune sensor, activating AP-1 and NF-κB signaling pathways.

Purpose of the Study:

  • To investigate the role of the SPRY domain in rhesus macaque TRIM5α's immune signaling and antiviral functions.
  • To elucidate the specific signaling pathways regulated by the SPRY domain.
  • To understand the mechanism of TRIM5α-mediated auto-ubiquitination and its impact on signaling.

Main Methods:

  • Site-directed mutagenesis to assess the role of the SPRY domain in signaling.
  • Western blotting and reporter assays to measure AP-1 and NF-κB activation.
  • Ubiquitination assays to analyze TRIM5α auto-ubiquitination patterns.

Main Results:

  • The SPRY domain of rhesus macaque TRIM5α is crucial for AP-1 activation but not NF-κB activation.
  • AP-1 activation is dependent on the β-sheet structure within the SPRY domain.
  • SPRY-mediated auto-ubiquitination, specifically Lys27-linked and Met1-linked polyubiquitination, is essential for AP-1 activation.
  • TRIM5α's signaling function correlates positively with its retroviral restriction activity.

Conclusions:

  • The SPRY domain plays a critical role in regulating TRIM5α's immune signaling, particularly AP-1 activation.
  • SPRY-mediated auto-ubiquitination is a key mechanism linking TRIM5α structure to its signaling output.
  • These findings enhance our understanding of TRIM5α's multifaceted antiviral mechanisms.
Keywords:
TAB2TAK1TRIM5alphaantiviral responseauto-ubiquitination

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