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Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer
SMURF2, an E3 ubiquitin ligase and suggested tumor suppressor, operates in normal cells to prevent genomic instability and carcinogenesis. However, the mechanisms underlying SMURF2 inactivation in human malignancies remain elusive, as SMURF2 is rarely found mutated or deleted in cancers. We hypothes...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521037/ https://www.ncbi.nlm.nih.gov/pubmed/31003445 http://dx.doi.org/10.3390/cancers11040556 |
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author | Emanuelli, Andrea Manikoth Ayyathan, Dhanoop Koganti, Praveen Shah, Pooja Anil Apel-Sarid, Liat Paolini, Biagio Detroja, Rajesh Frenkel-Morgenstern, Milana Blank, Michael |
author_facet | Emanuelli, Andrea Manikoth Ayyathan, Dhanoop Koganti, Praveen Shah, Pooja Anil Apel-Sarid, Liat Paolini, Biagio Detroja, Rajesh Frenkel-Morgenstern, Milana Blank, Michael |
author_sort | Emanuelli, Andrea |
collection | PubMed |
description | SMURF2, an E3 ubiquitin ligase and suggested tumor suppressor, operates in normal cells to prevent genomic instability and carcinogenesis. However, the mechanisms underlying SMURF2 inactivation in human malignancies remain elusive, as SMURF2 is rarely found mutated or deleted in cancers. We hypothesized that SMURF2 might have a distinct molecular biodistribution in cancer versus normal cells and tissues. The expression and localization of SMURF2 were analyzed in 666 human normal and cancer tissues, with primary focus on prostate and breast tumors. These investigations were accompanied by SMURF2 gene expression analyses, subcellular fractionation and biochemical studies, including SMURF2’s interactome analysis. We found that while in normal cells and tissues SMURF2 has a predominantly nuclear localization, in prostate and aggressive breast carcinomas SMURF2 shows a significantly increased cytoplasmic sequestration, associated with the disease progression. Mechanistic studies showed that the nuclear export machinery was not involved in cytoplasmic accumulation of SMURF2, while uncovered that its stability is markedly increased in the cytoplasmic compartment. Subsequent interactome analyses pointed to 14-3-3s as SMURF2 interactors, which could potentially affect its localization. These findings link the distorted expression of SMURF2 to human carcinogenesis and suggest the alterations in SMURF2 localization as a potential mechanism obliterating its tumor suppressor activities. |
format | Online Article Text |
id | pubmed-6521037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65210372019-05-31 Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer Emanuelli, Andrea Manikoth Ayyathan, Dhanoop Koganti, Praveen Shah, Pooja Anil Apel-Sarid, Liat Paolini, Biagio Detroja, Rajesh Frenkel-Morgenstern, Milana Blank, Michael Cancers (Basel) Article SMURF2, an E3 ubiquitin ligase and suggested tumor suppressor, operates in normal cells to prevent genomic instability and carcinogenesis. However, the mechanisms underlying SMURF2 inactivation in human malignancies remain elusive, as SMURF2 is rarely found mutated or deleted in cancers. We hypothesized that SMURF2 might have a distinct molecular biodistribution in cancer versus normal cells and tissues. The expression and localization of SMURF2 were analyzed in 666 human normal and cancer tissues, with primary focus on prostate and breast tumors. These investigations were accompanied by SMURF2 gene expression analyses, subcellular fractionation and biochemical studies, including SMURF2’s interactome analysis. We found that while in normal cells and tissues SMURF2 has a predominantly nuclear localization, in prostate and aggressive breast carcinomas SMURF2 shows a significantly increased cytoplasmic sequestration, associated with the disease progression. Mechanistic studies showed that the nuclear export machinery was not involved in cytoplasmic accumulation of SMURF2, while uncovered that its stability is markedly increased in the cytoplasmic compartment. Subsequent interactome analyses pointed to 14-3-3s as SMURF2 interactors, which could potentially affect its localization. These findings link the distorted expression of SMURF2 to human carcinogenesis and suggest the alterations in SMURF2 localization as a potential mechanism obliterating its tumor suppressor activities. MDPI 2019-04-18 /pmc/articles/PMC6521037/ /pubmed/31003445 http://dx.doi.org/10.3390/cancers11040556 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Emanuelli, Andrea Manikoth Ayyathan, Dhanoop Koganti, Praveen Shah, Pooja Anil Apel-Sarid, Liat Paolini, Biagio Detroja, Rajesh Frenkel-Morgenstern, Milana Blank, Michael Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer |
title | Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer |
title_full | Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer |
title_fullStr | Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer |
title_full_unstemmed | Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer |
title_short | Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer |
title_sort | altered expression and localization of tumor suppressive e3 ubiquitin ligase smurf2 in human prostate and breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521037/ https://www.ncbi.nlm.nih.gov/pubmed/31003445 http://dx.doi.org/10.3390/cancers11040556 |
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