Mutual regulation between deubiquitinase CYLD and retroviral oncoprotein Tax

Cell & Bioscience

Shao-Cong Sun¹  Minying Zhang¹  Xuefeng Wu¹ 

[1] Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston TX 77030, USA

关键词: NF-κB;    IKK;    ubiquitination;    Tax;    HTLV;    CYLD;   

Others  :  793961
DOI  :  10.1186/2045-3701-1-27

 received in 2011-06-23, accepted in 2011-08-08,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Wu et al; licensee BioMed Central Ltd.

【 图 表 】

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