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dc.contributor.authorDeshmukh, Dhanraj
dc.contributor.authorXu, Jin
dc.contributor.authorYang, Xi
dc.contributor.authorShimelis, Hermela
dc.contributor.authorFang, Shengyun
dc.contributor.authorQiu, Yun
dc.date.accessioned2022-04-26T12:47:23Z
dc.date.available2022-04-26T12:47:23Z
dc.date.issued2022-04-06
dc.identifier.urihttp://hdl.handle.net/10713/18659
dc.description.abstractThe cyclin-dependent kinase inhibitor p27 (Kip1) is an important regulator of the G1/S checkpoint. It is degraded by the SCF-SKP2 complex in late G1 thereby allowing cells to progress to the S phase. Here we investigated the role of the E3 ubiquitin ligase RNF6 (Ring Finger Protein 6) in cell cycle progression in prostate cancer cells. Our data demonstrate that RNF6 can promote cell cycle progression by reducing the levels of p27. Knockdown of RNF6 led to an increase in the stability of p27 and to the arrest of cells in the G1 phase. RNF6 interacted with p27 via its KIL domain and this interaction was found to be phosphorylation independent. RNF6 enhanced ubiquitination and subsequent degradation of p27 in the early G0/G1 phase of the cell cycle. Knockdown of RNF6 expression by short hairpin RNA led to inhibition of the CDK2/Cyclin E complex thereby reducing phosphorylation of Retinoblastoma protein (Rb) and to a subsequent decrease in cell cycle progression and proliferation. Our data suggest that RNF6 acts as a negative regulator for p27kip1 leading to its proteasome-dependent degradation in the early G0/G1 phase of the cell cycle.en_US
dc.description.urihttps://doi.org/10.3390/pharmaceutics14040802en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofPharmaceuticsen_US
dc.subjectRNF6en_US
dc.subjectcell cycleen_US
dc.subjectp27en_US
dc.subjectprostate canceren_US
dc.titleRegulation of p27 (Kip1) by Ubiquitin E3 Ligase RNF6.en_US
dc.typeArticleen_US
dc.identifier.doi10.3390/pharmaceutics14040802
dc.identifier.pmid35456636
dc.source.journaltitlePharmaceutics
dc.source.volume14
dc.source.issue4
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countrySwitzerland


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