Abstract
Background: Oncoprotein Tax, encoded by the human T-cell leukemia virus type 1 (HTLV1), persistently induces NF-κB activation, which contributes to HTLV1-mediated T-cell transformation. Recent studies suggest that the signaling function of Tax requires its ubiquitination, although how the Tax ubiquitination is regulated remains unclear.Results: We show here that the deubiquitinase CYLD physically interacts with Tax and negatively regulates the ubiquitination of this viral protein. This function of CYLD is associated with inhibition of Tax-mediated activation of IKK although not that of Tak1. Interestingly, CYLD undergoes constitutive phosphorylation in HTLV1-transformed T cells, a mechanism known to inactivate the catalytic activity of CYLD. Consistently, a phospho-mimetic CYLD mutant fails to inhibit Tax ubiquitination.Conclusion: These findings suggest that CYLD negatively regulates the signaling function of Tax through inhibition of Tax ubiquitination. Conversely, induction of CYLD phosphorylation may serve as a mechanism by which HTLV1 overrides the inhibitory function of CYLD, leading to the persistent activation of NF-κB.
Original language | English (US) |
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Article number | 27 |
Journal | Cell and Bioscience |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - Aug 8 2011 |
Keywords
- CYLD
- HTLV
- IKK
- NF-κ≥B
- Tax
- Ubiquitination
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
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- Flow Cytometry and Cellular Imaging Facility