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Smurf1 regulation of DAB2IP controls cell proliferation and migration

Tumor cell proliferation, survival and migration are regulated by the deletion of ovarian carcinoma 2/disabled homolog 2 (DOC-2/DAB2) interacting protein (DAB2IP), a tumor suppressor that serves as a scaffold protein for H-Ras and TRAF2. Importantly, the oncogenic histone methyl-transferase EZH2 epi...

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Autores principales: Li, Xiaoning, Dai, Xiangpeng, Wan, Lixin, Inuzuka, Hiroyuki, Sun, Liankun, North, Brian J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041964/
https://www.ncbi.nlm.nih.gov/pubmed/27036023
http://dx.doi.org/10.18632/oncotarget.8424
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author Li, Xiaoning
Dai, Xiangpeng
Wan, Lixin
Inuzuka, Hiroyuki
Sun, Liankun
North, Brian J.
author_facet Li, Xiaoning
Dai, Xiangpeng
Wan, Lixin
Inuzuka, Hiroyuki
Sun, Liankun
North, Brian J.
author_sort Li, Xiaoning
collection PubMed
description Tumor cell proliferation, survival and migration are regulated by the deletion of ovarian carcinoma 2/disabled homolog 2 (DOC-2/DAB2) interacting protein (DAB2IP), a tumor suppressor that serves as a scaffold protein for H-Ras and TRAF2. Importantly, the oncogenic histone methyl-transferase EZH2 epigenetically down-regulates DAB2IP in a variety of tumors. Recently, we demonstrated that DAB2IP is negatively regulated by Akt-dependent phosphorylation and SCF(Fbw7)-mediated degradation. Here, we further identify the oncoprotein Smurf1, an E3-ubiquitin ligase, as a novel negative regulator of DAB2IP. Smurf1-mediated cellular proliferation and migration are largely dependent on the presence of DAB2IP, suggesting that DAB2IP is a key effector molecule of Smurf1 oncogenic function. Additionally, we identify that similar to DAB2IP, Smurf1 is also a target of phosphorylation by both Akt1 and Akt2 kinases, which enhances Smurf1 abundance, leading to a reduction in DAB2IP. Given the role of DAB2IP in tumorigenesis and metastasis, our data identify Smurf1 as an upstream oncogenic factor that negatively regulates DAB2IP to govern aberrant cell growth and migration.
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spelling pubmed-50419642016-10-10 Smurf1 regulation of DAB2IP controls cell proliferation and migration Li, Xiaoning Dai, Xiangpeng Wan, Lixin Inuzuka, Hiroyuki Sun, Liankun North, Brian J. Oncotarget Research Paper Tumor cell proliferation, survival and migration are regulated by the deletion of ovarian carcinoma 2/disabled homolog 2 (DOC-2/DAB2) interacting protein (DAB2IP), a tumor suppressor that serves as a scaffold protein for H-Ras and TRAF2. Importantly, the oncogenic histone methyl-transferase EZH2 epigenetically down-regulates DAB2IP in a variety of tumors. Recently, we demonstrated that DAB2IP is negatively regulated by Akt-dependent phosphorylation and SCF(Fbw7)-mediated degradation. Here, we further identify the oncoprotein Smurf1, an E3-ubiquitin ligase, as a novel negative regulator of DAB2IP. Smurf1-mediated cellular proliferation and migration are largely dependent on the presence of DAB2IP, suggesting that DAB2IP is a key effector molecule of Smurf1 oncogenic function. Additionally, we identify that similar to DAB2IP, Smurf1 is also a target of phosphorylation by both Akt1 and Akt2 kinases, which enhances Smurf1 abundance, leading to a reduction in DAB2IP. Given the role of DAB2IP in tumorigenesis and metastasis, our data identify Smurf1 as an upstream oncogenic factor that negatively regulates DAB2IP to govern aberrant cell growth and migration. Impact Journals LLC 2016-03-27 /pmc/articles/PMC5041964/ /pubmed/27036023 http://dx.doi.org/10.18632/oncotarget.8424 Text en Copyright: © 2016 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Li, Xiaoning
Dai, Xiangpeng
Wan, Lixin
Inuzuka, Hiroyuki
Sun, Liankun
North, Brian J.
Smurf1 regulation of DAB2IP controls cell proliferation and migration
title Smurf1 regulation of DAB2IP controls cell proliferation and migration
title_full Smurf1 regulation of DAB2IP controls cell proliferation and migration
title_fullStr Smurf1 regulation of DAB2IP controls cell proliferation and migration
title_full_unstemmed Smurf1 regulation of DAB2IP controls cell proliferation and migration
title_short Smurf1 regulation of DAB2IP controls cell proliferation and migration
title_sort smurf1 regulation of dab2ip controls cell proliferation and migration
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041964/
https://www.ncbi.nlm.nih.gov/pubmed/27036023
http://dx.doi.org/10.18632/oncotarget.8424
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