WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP)
WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP)
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DOI：
10.1073/pnas.0610275104
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发表时间：
2007-01-16
影响因子：
11.1
通讯作者：
Ramesh, Narayanaswamy
中科院分区：
文献类型：
--
作者：
de la Fuente, Miguel A.;Sasahara, Yoji;Ramesh, Narayanaswamy
Wiskott-Aldrich综合征蛋白（WASP）与WASP相互作用蛋白（WASP-interacting protein，WASP）形成复合物。WASP水平，但不是mRNA水平，在T细胞中的严重减少，从T-/-小鼠，并增加了在这些细胞中引入的β-内酰胺酶。WASP结合结构域的钙蛋白酶在体外被证明可以保护WASP免受降解。用蛋白酶体抑制剂MG 132和硼替佐米治疗，增加了WASP水平，在T细胞中，从T-/-小鼠和T和B淋巴细胞中，从两个WAS患者的错义突变（R86 H和T45 M），破坏WASP结合。钙蛋白酶抑制剂钙肽酶增加了WASP患者活化T和B细胞中的WASP水平，但在患者或BALB/c小鼠的原代T细胞中没有。尽管蛋白酶体抑制剂能够增加WASP水平，但不能纠正R86 H WAS患者T细胞中受损的IL-2基因表达和低F-肌动蛋白含量。这些结果表明，β-淀粉酶稳定WASP，并表明它可能对其功能也很重要。
Wiskott-Aldrich syndrome protein (WASP) is in a complex with WASP-interacting protein (WIP). WASP levels, but not mRNA levels, were severely diminished in T cells from WIP-/- mice and were increased by introduction of WIP in these cells. The WASP binding domain of WIP was shown to protect WASP from degradation by calpain in vitro. Treatment with the proteasome inhibitors MG132 and bortezomib increased WASP levels in T cells from WIP-/- mice and in T and B lymphocytes from two WAS patients with missense mutations (R86H and T45M) that disrupt WIP binding. The calpain inhibitor calpeptin increased WASP levels in activated T and B cells from the WASP patients, but not in primary T cells from the patients or from WIP-/- mice. Despite its ability to increase WASP levels proteasome inhibition did not correct the impaired IL-2 gene expression and low F-actin content in T cells from the R86H WAS patient. These results demonstrate that WIP stabilizes WASP and suggest that it may also be important for its function.