TAX1BP1, a ubiquitin-binding adaptor protein in innate immunity and beyond

The innate immune system senses and protects against invading microorganisms and endogenous danger signals by triggering inflammatory and antimicrobial responses. However, dysregulation of these pathways, which involve the transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) 3, can lead to severe inflammatory diseases. Tax1-binding protein 1 (TAX1BP1) plays a key role in the negative regulation of NF-κB and IRF3 signaling by acting in concert with the ubiquitin-editing enzyme A20. In addition to regulating A20 function in anti-inflammatory and antiviral signaling pathways, TAX1BP1 also coordinates its antiapoptotic activities. Moreover, TAX1BP1 can also function as a transcriptional coactivator for nuclear receptors and viral transactivators. In this review, we discuss these findings in light of the emerging role of TAX1BP1 as a ubiquitin-binding adaptor protein.