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MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration.

ABSTRACT: Our previous studies have shown that the HECT E3 ubiquitin ligase NEDD4 and kinase MEKK5 both play an essential role in lung cancer migration. A report predicts that MEKK5 may be ubiquitinated by NEDD4; however, interaction of MEKK5 with NEDD4 and ubiquitination of MEKK5 by NEDD4 have not been characterized. In this report, we show that NEDD4 interacts with MEKK5 through a conserved WW3 domain by the co-immunoprecipitation and the GST-pulldown assays. The ubiquitination assay indicates that MEKK5 is not a ubiquitination substrate of NEDD4, but negatively regulates NEDD4-mediated ubiquitination. Furthermore, overexpression of MEKK5 significantly reduced the NEDD4-promoted lung cancer cell migration. Taken together, our studies have defined an inhibitory role of MEKK5 in regulation of NEDD4-mediated ubiquitination.

SUBMITTER: Sun A

PROVIDER: S-EPMC8620495 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration.

Sun Aiqin A Zhu Jun J Xia Song S Li Yanling Y Wu Tiantian T Shao Genbao G Yang Wannian W Lin Qiong Q

Life (Basel, Switzerland) 20211029 11

Our previous studies have shown that the HECT E3 ubiquitin ligase NEDD4 and kinase MEKK5 both play an essential role in lung cancer migration. A report predicts that MEKK5 may be ubiquitinated by NEDD4; however, interaction of MEKK5 with NEDD4 and ubiquitination of MEKK5 by NEDD4 have not been characterized. In this report, we show that NEDD4 interacts with MEKK5 through a conserved WW3 domain by the co-immunoprecipitation and the GST-pulldown assays. The ubiquitination assay indicates that MEKK ...[more]

PMID: 34833029

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