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Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration
PML protein plays important roles in regulating cellular homeostasis. It forms PML nuclear bodies (PML-NBs) that act like nuclear relay stations and participate in many cellular functions. In this study, we have examined the proteome of mouse embryonic fibroblasts (MEFs) derived from normal (PML(+/+...
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/PMC3605454/ https://www.ncbi.nlm.nih.gov/pubmed/23555679 http://dx.doi.org/10.1371/journal.pone.0059477 |
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author | Tang, Mei Kuen Liang, Yong Jia Chan, John Yeuk Hon Wong, Sing Wan Chen, Elve Yao, Yao Gan, Jingyi Xiao, Lihai Leung, Hin Cheung Kung, Hsiang Fu Wang, Hua Lee, Kenneth Ka Ho |
author_facet | Tang, Mei Kuen Liang, Yong Jia Chan, John Yeuk Hon Wong, Sing Wan Chen, Elve Yao, Yao Gan, Jingyi Xiao, Lihai Leung, Hin Cheung Kung, Hsiang Fu Wang, Hua Lee, Kenneth Ka Ho |
author_sort | Tang, Mei Kuen |
collection | PubMed |
description | PML protein plays important roles in regulating cellular homeostasis. It forms PML nuclear bodies (PML-NBs) that act like nuclear relay stations and participate in many cellular functions. In this study, we have examined the proteome of mouse embryonic fibroblasts (MEFs) derived from normal (PML(+/+)) and PML knockout (PML(−/−)) mice. The aim was to identify proteins that were differentially expressed when MEFs were incapable of producing PML. Using comparative proteomics, total protein were extracted from PML(−/−) and PML(+/+) MEFs, resolved by two dimensional electrophoresis (2-DE) gels and the differentially expressed proteins identified by LC-ESI-MS/MS. Nine proteins (PML, NDRG1, CACYBP, CFL1, RSU1, TRIO, CTRO, ANXA4 and UBE2M) were determined to be down-regulated in PML(−/−) MEFs. In contrast, ten proteins (CIAPIN1, FAM50A, SUMO2 HSPB1 NSFL1C, PCBP2, YWHAG, STMN1, TPD52L2 and PDAP1) were found up-regulated. Many of these differentially expressed proteins play crucial roles in cell adhesion, migration, morphology and cytokinesis. The protein profiles explain why PML(−/−) and PML(+/+) MEFs were morphologically different. In addition, we demonstrated PML(−/−) MEFs were less adhesive, proliferated more extensively and migrated significantly slower than PML(+/+) MEFs. NDRG1, a protein that was down-regulated in PML(−/−) MEFs, was selected for further investigation. We determined that silencing NDRG1expression in PML(+/+) MEFs increased cell proliferation and inhibited PML expression. Since NDRG expression was suppressed in PML(−/−) MEFs, this may explain why these cells proliferate more extensively than PML(+/+) MEFs. Furthermore, silencing NDRG1expression also impaired TGF-β1 signaling by inhibiting SMAD3 phosphorylation. |
format | Online Article Text |
id | pubmed-3605454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36054542013-04-03 Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration Tang, Mei Kuen Liang, Yong Jia Chan, John Yeuk Hon Wong, Sing Wan Chen, Elve Yao, Yao Gan, Jingyi Xiao, Lihai Leung, Hin Cheung Kung, Hsiang Fu Wang, Hua Lee, Kenneth Ka Ho PLoS One Research Article PML protein plays important roles in regulating cellular homeostasis. It forms PML nuclear bodies (PML-NBs) that act like nuclear relay stations and participate in many cellular functions. In this study, we have examined the proteome of mouse embryonic fibroblasts (MEFs) derived from normal (PML(+/+)) and PML knockout (PML(−/−)) mice. The aim was to identify proteins that were differentially expressed when MEFs were incapable of producing PML. Using comparative proteomics, total protein were extracted from PML(−/−) and PML(+/+) MEFs, resolved by two dimensional electrophoresis (2-DE) gels and the differentially expressed proteins identified by LC-ESI-MS/MS. Nine proteins (PML, NDRG1, CACYBP, CFL1, RSU1, TRIO, CTRO, ANXA4 and UBE2M) were determined to be down-regulated in PML(−/−) MEFs. In contrast, ten proteins (CIAPIN1, FAM50A, SUMO2 HSPB1 NSFL1C, PCBP2, YWHAG, STMN1, TPD52L2 and PDAP1) were found up-regulated. Many of these differentially expressed proteins play crucial roles in cell adhesion, migration, morphology and cytokinesis. The protein profiles explain why PML(−/−) and PML(+/+) MEFs were morphologically different. In addition, we demonstrated PML(−/−) MEFs were less adhesive, proliferated more extensively and migrated significantly slower than PML(+/+) MEFs. NDRG1, a protein that was down-regulated in PML(−/−) MEFs, was selected for further investigation. We determined that silencing NDRG1expression in PML(+/+) MEFs increased cell proliferation and inhibited PML expression. Since NDRG expression was suppressed in PML(−/−) MEFs, this may explain why these cells proliferate more extensively than PML(+/+) MEFs. Furthermore, silencing NDRG1expression also impaired TGF-β1 signaling by inhibiting SMAD3 phosphorylation. Public Library of Science 2013-03-21 /pmc/articles/PMC3605454/ /pubmed/23555679 http://dx.doi.org/10.1371/journal.pone.0059477 Text en © 2013 Tang 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 Tang, Mei Kuen Liang, Yong Jia Chan, John Yeuk Hon Wong, Sing Wan Chen, Elve Yao, Yao Gan, Jingyi Xiao, Lihai Leung, Hin Cheung Kung, Hsiang Fu Wang, Hua Lee, Kenneth Ka Ho Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration |
title | Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration |
title_full | Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration |
title_fullStr | Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration |
title_full_unstemmed | Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration |
title_short | Promyelocytic Leukemia (PML) Protein Plays Important Roles in Regulating Cell Adhesion, Morphology, Proliferation and Migration |
title_sort | promyelocytic leukemia (pml) protein plays important roles in regulating cell adhesion, morphology, proliferation and migration |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605454/ https://www.ncbi.nlm.nih.gov/pubmed/23555679 http://dx.doi.org/10.1371/journal.pone.0059477 |
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