ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2
DC Field | Value | Language |
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dc.contributor.author | Tran, N.N.Q. | - |
dc.contributor.author | Chun, Kwang-Hoon | - |
dc.date.accessioned | 2021-09-06T00:41:38Z | - |
dc.date.available | 2021-09-06T00:41:38Z | - |
dc.date.created | 2021-08-19 | - |
dc.date.issued | 2021-08 | - |
dc.identifier.issn | 1420-3049 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82072 | - |
dc.description.abstract | KD025, a ROCK2 isoform-specific inhibitor, has an anti-adipogenic activity which is not mediated by ROCK2 inhibition. To identify the target, we searched binding targets of KD025 by using the KINOMEscan™ screening platform, and we identified casein kinase 2 (CK2) as a novel target. KD025 showed comparable binding affinity to CK2α (Kd = 128 nM). By contrast, CK2 inhibitor CX-4945 and ROCK inhibitor fasudil did not show such cross-reactivity. In addition, KD025 effectively inhibited CK2 at a nanomolar concentration (IC50 = 50 nM). We examined if the inhibitory effect of KD025 on adipocyte differentiation is through the inhibition of CK2. Both CX-4945 and KD025 suppressed the generation of lipid droplets and the expression of proadipogenic genes Pparg and Cebpa in 3T3-L1 cells during adipocyte differentiation. Fasudil exerted no significant effect on the quantity of lipid droplets, but another ROCK inhibitor Y-27632 increased the expression of Pparg and Cebpa. Both CX-4945 and KD025 acted specifically in the middle stage (days 1–3) but were ineffective when treated at days 0–1 or the late stages, indicating that CX-4945 and KD025 may regulate the same target, CK2. The mRNA and protein levels of CK2α and CK2β generally decreased in 3T3-L1 cells at day 2 but recovered thereafter. Other well-known CK2 inhibitors DMAT and quinalizarin inhibited effectively the differentiation of 3T3-L1 cells. Taken together, the results of this study confirmed that KD025 inhibits ROCK2 and CK2, and that the inhibitory effect on adipocyte differentiation is through the inhibition of CK2. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.relation.isPartOf | Molecules | - |
dc.title | ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2 | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000690191300001 | - |
dc.identifier.doi | 10.3390/molecules26164747 | - |
dc.identifier.bibliographicCitation | Molecules, v.26, no.16 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85112317353 | - |
dc.citation.title | Molecules | - |
dc.citation.volume | 26 | - |
dc.citation.number | 16 | - |
dc.contributor.affiliatedAuthor | Tran, N.N.Q. | - |
dc.contributor.affiliatedAuthor | Chun, Kwang-Hoon | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Adipocyte differentiation | - |
dc.subject.keywordAuthor | Belumosudil | - |
dc.subject.keywordAuthor | Casein kinase | - |
dc.subject.keywordAuthor | CK2 | - |
dc.subject.keywordAuthor | KD025 | - |
dc.subject.keywordAuthor | ROCK2 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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