Abstract:
:The ubiquitin-editing enzyme A20 is a critical negative regulator of inflammation and cytokine-mediated activation of the transcription factor NF-kappaB; however, little is known about the mechanisms of A20-mediated inactivation of signaling intermediates such as RIP1. Here we demonstrate that the regulatory molecule TAX1BP1 recruited the E3 ligase Itch to A20 via two 'PPXY' motifs. Itch was essential for the termination of tumor necrosis factor receptor signaling by controlling A20-mediated recruitment and inactivation of RIP1. Furthermore, the Tax oncoprotein of human T cell leukemia virus type I targeted this complex for inactivation by disrupting the interaction among TAX1BP1, A20 and Itch. Thus, our studies show a previously unappreciated complexity of A20 substrate recognition and inactivation whereby TAX1BP1 and Itch function as essential subunits of an A20 ubiquitin-editing complex.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Shembade N,Harhaj NS,Parvatiyar K,Copeland NG,Jenkins NA,Matesic LE,Harhaj EWdoi
10.1038/ni1563subject
Has Abstractpub_date
2008-03-01 00:00:00pages
254-62issue
3eissn
1529-2908issn
1529-2916pii
ni1563journal_volume
9pub_type
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