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

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 chara...

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Autores principales: Aiqin Sun, Jun Zhu, Song Xia, Yanling Li, Tiantian Wu, Genbao Shao, Wannian Yang, Qiong Lin
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/e3ace83e789243b6a19e6afe8c11528f
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spelling oai:doaj.org-article:e3ace83e789243b6a19e6afe8c11528f2021-11-25T18:10:43ZMEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration10.3390/life111111532075-1729https://doaj.org/article/e3ace83e789243b6a19e6afe8c11528f2021-10-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1153https://doaj.org/toc/2075-1729Our 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.Aiqin SunJun ZhuSong XiaYanling LiTiantian WuGenbao ShaoWannian YangQiong LinMDPI AGarticleMEKK5NEDD4E3 ubiquitin ligaseubiquitinationcell migrationScienceQENLife, Vol 11, Iss 1153, p 1153 (2021)
institution DOAJ
collection DOAJ
language EN
topic MEKK5
NEDD4
E3 ubiquitin ligase
ubiquitination
cell migration
Science
Q
spellingShingle MEKK5
NEDD4
E3 ubiquitin ligase
ubiquitination
cell migration
Science
Q
Aiqin Sun
Jun Zhu
Song Xia
Yanling Li
Tiantian Wu
Genbao Shao
Wannian Yang
Qiong Lin
MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration
description 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.
format article
author Aiqin Sun
Jun Zhu
Song Xia
Yanling Li
Tiantian Wu
Genbao Shao
Wannian Yang
Qiong Lin
author_facet Aiqin Sun
Jun Zhu
Song Xia
Yanling Li
Tiantian Wu
Genbao Shao
Wannian Yang
Qiong Lin
author_sort Aiqin Sun
title MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration
title_short MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration
title_full MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration
title_fullStr MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration
title_full_unstemmed MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration
title_sort mekk5 interacts with and negatively regulates the e3 ubiquitin ligase nedd4 for mediating lung cancer cell migration
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/e3ace83e789243b6a19e6afe8c11528f
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