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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2021
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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) |
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MEKK5 NEDD4 E3 ubiquitin ligase ubiquitination cell migration Science Q |
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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 |
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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 |
work_keys_str_mv |
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