Itch attenuates CD4 T-cell proliferation in mice by limiting WBP2 protein stability.
Itch attenuates CD4 T-cell proliferation in mice by limiting WBP2 protein stability.
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DOI：
10.1002/eji.201948323
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发表时间：
2020-10
影响因子：
5.4
通讯作者：
Oliver PM
中科院分区：
文献类型：
--
作者：
Field NS;Elbulok OA;Dybas JM;Moser EK;Dar AA;Spruce LA;Fazelinia H;Seeholzer SH;Oliver PM
To mount an antipathogen response, CD4 T cells must undergo rapid cell proliferation; however, poorly controlled expansion can result in diseases such as autoimmunity. One important regulator of T-cell activity is the E3 ubiquitin ligase Itch. Itch deficient patients suffer from extensive autoinflammation. Similarly, Itch deficient mice exhibit inflammation characterized by high numbers of activated CD4 T cells. While the role of Itch in limiting CD4 T-cell cytokine production has been extensively studied, it is less clear whether and how Itch regulates proliferation of these cells. We determined that Itch deficient CD4 T cells are hyperproliferative in vitro and in vivo, due to increased S phase entry. Whole cell proteomics analysis of Itch deficient primary mouse CD4 T cells revealed increased abundance of the β-catenin coactivator WW domain-binding protein 2 (WBP2). Furthermore, Itch deficient cells demonstrate increased WBP2 protein stability, and Itch and WBP2 interact in CD4 T cells. Knockdown of WBP2 in CD4 T cells caused reduced proliferation. Together, our data support that Itch attenuates CD4 T cell proliferation by promoting WBP2 degradation. This study identifies novel roles for Itch and WBP2 in regulating CD4 T cell proliferation, providing insight into how Itch may prevent inflammation.
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影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
DOI：
10.1007/978-1-0716-0266-9_19
发表时间：
2020
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Field NS;O'Leary CE;Dybas JM;Ding H;Oliver PM
通讯作者：
Oliver PM
影响因子：
32.4
作者：
Oliver, Paula M.;Cao, Xiao;Yang, Baoli
通讯作者：
Yang, Baoli
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
2
作者：
Brittain, Helen K.;Feary, Johanna;Wilson, Louise C.
通讯作者：
Wilson, Louise C.