NDLI: Smurf1 regulation of DAB2IP controls cell proliferation and migration

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Smurf1 regulation of DAB2IP controls cell proliferation and migration

Content Provider	Semantic Scholar
Author	Li, Xiaoning Dai, Xiangpeng Wan, Lixin Inuzuka, Hiroyuki Sun, Liankun
Copyright Year	2016
Abstract	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.
Starting Page	26057
Ending Page	26069
Page Count	13
File Format	PDF HTM / HTML
PubMed reference number	27036023
Alternate Webpage(s)	https://doi.org/10.18632/oncotarget.8424
DOI	10.18632/oncotarget.8424
Journal	Oncotarget
Volume Number	7
Language	English
Access Restriction	Open
Subject Keyword	Carcinogenesis Catabolism Cell Proliferation DAB2IP gene Deletion Mutation Fusion Proteins, bcr-abl Histones Leukemia, B-Cell Ligase Neoplasms Oncogene Proteins Ovarian Carcinoma Proto-Oncogene Proteins c-akt SMURF1 gene TNF receptor-associated factor 2 Transferase Tumor Suppressor Genes cell growth negative regulation of methyl-branched fatty acid biosynthetic process
Content Type	Text
Resource Type	Article

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