Wan Ying, Petris Michael J, Peck Scott C
Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
FEBS Lett. 2014 Aug 25;588(17):2928-35. doi: 10.1016/j.febslet.2014.05.043. Epub 2014 Jun 6.
Free zinc is required for proper lipopolysaccharide (LPS)-stimulated signaling, but potential sites of action in the pathway have not been defined. In this work, we provide in vitro and ex vivo evidence that zinc is not required for phosphorylation or ubiquitylation of IRAK1, a kinase functioning early in the TLR4 pathway. However, degradation of ubiquitylated IRAK1 occurred via a zinc-dependent, proteasome-independent pathway. These results provide evidence of a novel site of action for zinc during TLR4-mediated inflammatory responses.
适当的脂多糖（LPS）刺激信号传导需要游离锌，但该途径中的潜在作用位点尚未明确。在这项研究中，我们提供了体外和体内证据，表明锌对于IRAK1（一种在TLR4途径中早期起作用的激酶）的磷酸化或泛素化不是必需的。然而，泛素化的IRAK1的降解是通过锌依赖性、蛋白酶体非依赖性途径发生的。这些结果提供了锌在TLR4介导的炎症反应中一个新的作用位点的证据。
