HTLV-1 tax-induced NFκB activation is independent of Lys-63-linked-type polyubiquitination
HTLV-1 tax-induced NFκB activation is independent of Lys-63-linked-type polyubiquitination
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DOI：
10.1016/j.bbrc.2007.03.125
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发表时间：
2007-05-25
影响因子：
3.1
通讯作者：
Inoue, Jun-ichiro
中科院分区：
文献类型：
--
作者：
Gohda, Jin;Irisawa, Masato;Inoue, Jun-ichiro
人T细胞白血病病毒1型（HTLV-1）紫杉醇诱导的核因子-κ B（NF κ B）活化被认为在T细胞转化和成人T细胞白血病发病中起关键作用。然而，Tax诱导NF κ B B活化的分子机制仍不清楚。丝裂原活化蛋白激酶（MAPK 3 Ks）成员之一TAK 1在丝氨酸诱导的NF κ B活化中起关键作用，其涉及I κ B激酶复合物的非催化亚基NEMO的赖氨酸63连接（K63）多聚泛素化。在这里，我们表明，税收诱导NEMO的K63聚泛素化。然而，TAK 1对于Tax诱导的NF κ B B活化是无效的，并且K63多聚泛素链的去泛素化不能阻断Tax诱导的NF κ B B活化。此外，沉默其他MAP 3 K，包括MEKK 1、MEKK 3、NIK和TPL-2，不影响Tax诱导的NF κ B B活化。这些结果有力地表明，与细胞因子信号传导不同，Tax诱导的NF κ B B活化不涉及K63多聚泛素化介导的MAP 3 K活化。(c)2007年爱思唯尔公司All rights reserved.
Human T-cell leukemia virus type 1 (HTLV-1) Tax-induced activation of nuclear factor-kappa B (NF kappa B) is thought to play a critical role in T-cell transformation and onset of adult T-cell leukemia. However, the molecular mechanism of the Tax-induced NF kappa B activation remains unknown. One of the mitogen-activated protein kinase kinase kinses (MAP3Ks) members, TAK1, plays a critical role in cytokine-induced activation of NF kappa B, which involves lysine 63-linked (K63) polyubiquitination of NEMO, a noncatalytic subunit of the I kappa B kinase complex. Here we show that Tax induces K63 polyubiquitination of NEMO. However, TAK1 is dispensable for Tax-induced NF kappa B activation, and deubiquitination of the K63 polyubiquitin chain failed to block Tax-induced NF kappa B activation. In addition, silencing of other MAP3Ks, including MEKK1, MEKK3, NIK, and TPL-2, did not affect Tax-induced NF kappa B activation. These results strongly suggest that unlike cytokine signaling, Tax-induced NF kappa B activation does not involve K63 polyubiquitination-mediated MAP3K activation. (c) 2007 Elsevier Inc. All rights reserved.