Mutual regulation of conventional protein kinase C and a ubiquitin ligase complex
Mutual regulation of conventional protein kinase C and a ubiquitin ligase complex
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DOI：
10.1016/j.bbrc.2006.09.163
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发表时间：
2006-12-15
影响因子：
3.1
通讯作者：
Iwai, Kazuhiro
中科院分区：
文献类型：
--
作者：
Nakamura, Munehiro;Tokunaga, Fuminori;Iwai, Kazuhiro
佛波酯介导的激活后，蛋白激酶 C (PKC) 的几种亚型会被泛素蛋白酶体途径降解。然而，人们对靶向激活 PKC 的泛素连接酶 (E3) 知之甚少。我们最近表明，由 HOIL-1L 和 HOW (LUBAC) 组成的 E3 复合物生成线性多聚泛素链并诱导模型底物的蛋白酶体降解。 HOIL-1L 也被定性为 PKC 结合蛋白。在这里，我们表明 LUBAC 优先结合激活的常规 PKC 及其组成型活性突变体。 LUBAC 在体外有效地泛素化活化的 PKC，并且在 HOIL-1L 缺陷细胞中活化的 PKC α 的降解被延迟。相反，PKC 激活诱导 HOIL-1L 裂解并导致 LUBAC 连接酶活性下调。这些结果表明，LUBAC 是激活的常规 PKC 的 E3，并且 PKC 和 LUBAC 相互调节以实现正确的 PKC 信号传导。 (c) 2006 Elsevier Inc. 保留所有权利。
Several isoforms of protein kinase C (PKC) are degraded by the ubiquitin-proteasome pathway after phorbol ester-mediated activation. However, little is known about the ubiquitin ligase (E3) that targets activated PKCs. We recently showed that an E3 complex composed of HOIL-1L and HOW (LUBAC) generates linear polyubiquitin chains and induces the proteasomal degradation of a model substrate. HOIL-1L has also been characterized as a PKC-binding protein. Here we show that LUBAC preferentially binds activated conventional PKCs and their constitutively active mutants. LUBAC efficiently ubiquitinated activated PKC in vitro, and degradation of activated PKC alpha was delayed in HOIL-1L-deficient cells. Conversely, PKC activation induced cleavage of HOIL-1L and led to down-regulation of the ligase activity of LUBAC. These results indicate that LUBAC is an E3 for activated conventional PKC, and that PKC and LUBAC regulate each other for proper PKC signaling. (c) 2006 Elsevier Inc. All rights reserved.