Smurf1 regulation of DAB2IP controls cell proliferation and migration

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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Main Authors: Li, Xiaoning, Dai, Xiangpeng, Wan, Lixin, Inuzuka, Hiroyuki, Sun, Liankun, North, Brian J.
Format: Online
Language:English
Published: Impact Journals LLC 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041964/
id pubmed-5041964
recordtype oai_dc
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. 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 SCFFbw7-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.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Li, Xiaoning
Dai, Xiangpeng
Wan, Lixin
Inuzuka, Hiroyuki
Sun, Liankun
North, Brian J.
spellingShingle Li, Xiaoning
Dai, Xiangpeng
Wan, Lixin
Inuzuka, Hiroyuki
Sun, Liankun
North, Brian J.
Smurf1 regulation of DAB2IP controls cell proliferation and migration
author_facet Li, Xiaoning
Dai, Xiangpeng
Wan, Lixin
Inuzuka, Hiroyuki
Sun, Liankun
North, Brian J.
author_sort Li, Xiaoning
title Smurf1 regulation of DAB2IP controls cell proliferation and migration
title_short 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_sort smurf1 regulation of dab2ip controls cell proliferation and migration
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 SCFFbw7-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.
publisher Impact Journals LLC
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041964/
_version_ 1613665633524776960

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