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Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells
The Zinc Finger (ZNF) 280B protein was identified as an unexpected target of an shRNA designed for sGCα1. Further analysis showed that these two proteins are connected in another way, with 280B up-regulation of sGCα1 expression. Knock-down and over-expression experiments showed that 280B serves pro-...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827277/ https://www.ncbi.nlm.nih.gov/pubmed/24236047 http://dx.doi.org/10.1371/journal.pone.0078766 |
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author | Gao, Shuai Hsieh, Chen-Lin Zhou, Jun Shemshedini, Lirim |
author_facet | Gao, Shuai Hsieh, Chen-Lin Zhou, Jun Shemshedini, Lirim |
author_sort | Gao, Shuai |
collection | PubMed |
description | The Zinc Finger (ZNF) 280B protein was identified as an unexpected target of an shRNA designed for sGCα1. Further analysis showed that these two proteins are connected in another way, with 280B up-regulation of sGCα1 expression. Knock-down and over-expression experiments showed that 280B serves pro-growth and pro-survival functions in prostate cancer. Surprisingly however, these pro-cancer functions of 280B are not mediated by sGCα1, which itself has similar functions in prostate cancer, but by down-regulated p53. The p53 protein is a second target of 280B in prostate cancer, but unlike sGCα1, p53 is down-regulated by 280B. 280B induces p53 nuclear export, leading to subsequent proteasomal degradation. The protein responsible for p53 regulation by 280B is Mdm2, the E3 ubiquitin ligase that promotes p53 degradation by inducing its nuclear export. We show here that 280B up-regulates expression of Mdm2 in prostate cancer cells, and this regulation is via the Mdm2 promoter. To demonstrate an in vivo relevance to this interaction, expression studies show that 280B protein levels are up-regulated in prostate cancer and these levels correspond to reduced levels of p53. Thus, by enhancing the expression of Mdm2, the uncharacterized 280B protein provides a novel mechanism of p53 suppression in prostate cancer. |
format | Online Article Text |
id | pubmed-3827277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38272772013-11-14 Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells Gao, Shuai Hsieh, Chen-Lin Zhou, Jun Shemshedini, Lirim PLoS One Research Article The Zinc Finger (ZNF) 280B protein was identified as an unexpected target of an shRNA designed for sGCα1. Further analysis showed that these two proteins are connected in another way, with 280B up-regulation of sGCα1 expression. Knock-down and over-expression experiments showed that 280B serves pro-growth and pro-survival functions in prostate cancer. Surprisingly however, these pro-cancer functions of 280B are not mediated by sGCα1, which itself has similar functions in prostate cancer, but by down-regulated p53. The p53 protein is a second target of 280B in prostate cancer, but unlike sGCα1, p53 is down-regulated by 280B. 280B induces p53 nuclear export, leading to subsequent proteasomal degradation. The protein responsible for p53 regulation by 280B is Mdm2, the E3 ubiquitin ligase that promotes p53 degradation by inducing its nuclear export. We show here that 280B up-regulates expression of Mdm2 in prostate cancer cells, and this regulation is via the Mdm2 promoter. To demonstrate an in vivo relevance to this interaction, expression studies show that 280B protein levels are up-regulated in prostate cancer and these levels correspond to reduced levels of p53. Thus, by enhancing the expression of Mdm2, the uncharacterized 280B protein provides a novel mechanism of p53 suppression in prostate cancer. Public Library of Science 2013-11-13 /pmc/articles/PMC3827277/ /pubmed/24236047 http://dx.doi.org/10.1371/journal.pone.0078766 Text en © 2013 Gao et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Gao, Shuai Hsieh, Chen-Lin Zhou, Jun Shemshedini, Lirim Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells |
title | Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells |
title_full | Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells |
title_fullStr | Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells |
title_full_unstemmed | Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells |
title_short | Zinc Finger 280B Regulates sGCα1 and p53 in Prostate Cancer Cells |
title_sort | zinc finger 280b regulates sgcα1 and p53 in prostate cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827277/ https://www.ncbi.nlm.nih.gov/pubmed/24236047 http://dx.doi.org/10.1371/journal.pone.0078766 |
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