Mutual regulation between deubiquitinase CYLD and retroviral oncoprotein Tax.
Mutual regulation between deubiquitinase CYLD and retroviral oncoprotein Tax.
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去泛素酶CYLD和逆转录病毒癌蛋白税之间的相互调节。
DOI：
10.1186/2045-3701-1-27
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发表时间：
2011-08-08
影响因子：
7.5
通讯作者：
Sun SC
中科院分区：
文献类型：
--
作者：
Wu X;Zhang M;Sun SC
人类T细胞白血病病毒1型(HTLV1)编码的癌蛋白TAX持续诱导核转录因子κB的激活，从而促进HTLV1介导的T细胞转化。最近的研究表明，税收的信号功能需要它的泛素化，尽管税收泛素化是如何调控的仍不清楚。我们在这里表明，去泛素酶CyLD物理上与TAX相互作用，并负向调节这种病毒蛋白的泛素化。CyLD的这一功能与抑制税收介导的IKK激活有关，但与Tak1无关。有趣的是，在HTLV1转化的T细胞中，CyLD经历了结构性的磷酸化，这是已知的使CyLD的催化活性失活的机制。一直以来，模拟磷酸的CyLD突变体都不能抑制税收泛素化。这些发现表明，CyLD通过抑制税收泛素化来负向调节税收的信号传递功能。相反，诱导CyLD的磷酸化可能是HTLV 1推翻CyLD的抑制功能，导致NF-κB持续激活的机制之一。
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. 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. 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.
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