{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:48:44Z","timestamp":1762102124000,"version":"3.38.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cytoplasmic linker protein 170 (CLIP170) is a CAP-Gly domain\u2013containing protein that is associated with the plus end of growing microtubules and implicated in various cellular processes, including the regulation of microtubule dynamics, cell migration, and intracellular transport. Our studies revealed a previously unrecognized property and role of CLIP170. We identified CLIP170 as one of the interacting partners of Brucella effector protein TcpB that negatively regulates TLR2 and TLR4 signaling. In this study, we demonstrate that CLIP170 interacts with the TLR2 and TLR4 adaptor protein TIRAP. Furthermore, our studies revealed that CLIP170 induces ubiquitination and subsequent degradation of TIRAP to negatively regulate TLR4-mediated proinflammatory responses. Overexpression of CLIP170 in mouse macrophages suppressed the LPS-induced expression of IL-6 and TNF-\u03b1 whereas silencing of endogenous CLIP170 potentiated the levels of proinflammatory cytokines. In vivo silencing of CLIP170 in C57BL\/6 mice by CLIP170-specific small interfering RNA enhanced LPS-induced IL-6 and TNF-\u03b1 expression. Furthermore, we found that LPS modulates the expression of CLIP170 in mouse macrophages. Overall, our experimental data suggest that CLIP170 serves as an intrinsic negative regulator of TLR4 signaling that targets TIRAP.<\/jats:p>","DOI":"10.4049\/jimmunol.1601559","type":"journal-article","created":{"date-parts":[[2017,12,8]],"date-time":"2017-12-08T17:50:16Z","timestamp":1512755416000},"page":"704-714","source":"Crossref","is-referenced-by-count":23,"title":["Cytoplasmic Linker Protein CLIP170 Negatively Regulates TLR4 Signaling by Targeting the TLR Adaptor Protein TIRAP"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3090-9456","authenticated-orcid":false,"given":"Padmaja","family":"Jakka","sequence":"first","affiliation":[{"name":"National Institute of Animal Biotechnology , Hyderabad, Telangana 500049,","place":["India"]},{"name":"Graduate Studies, Manipal University , Manipal, Karnataka 576104,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bindu","family":"Bhargavi","sequence":"additional","affiliation":[{"name":"National Institute of Animal Biotechnology , Hyderabad, Telangana 500049,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1788-0107","authenticated-orcid":false,"given":"Swapna","family":"Namani","sequence":"additional","affiliation":[{"name":"National Institute of Animal Biotechnology , Hyderabad, Telangana 500049,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subathra","family":"Murugan","sequence":"additional","affiliation":[{"name":"National Institute of Animal Biotechnology , Hyderabad, Telangana 500049,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Splitter","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2013Madison , Madison, WI 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9088-0029","authenticated-orcid":false,"given":"Girish","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"National Institute of Animal Biotechnology , Hyderabad, Telangana 500049,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"2025030610005637800_r1","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/90609","article-title":"Toll-like receptors: critical proteins linking innate and acquired immunity","volume":"2","author":"Akira","year":"2001","journal-title":"Nat. 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