Cargando…
Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation
Sox2 is a pluripotency transcription factor that as an oncogene can also regulate cell proliferation. Therefore, genes implicated in several different aspects of cell proliferation, such as the VRK1 chromatin-kinase, are candidates to be targets of Sox2. Sox 2 and VRK1 colocalize in nuclei of prolif...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917848/ https://www.ncbi.nlm.nih.gov/pubmed/27334688 http://dx.doi.org/10.1038/srep28532 |
_version_ | 1782439007901188096 |
---|---|
author | Moura, David S. Fernández, Isabel F. Marín-Royo, Gema López-Sánchez, Inmaculada Martín-Doncel, Elena Vega, Francisco M. Lazo, Pedro A. |
author_facet | Moura, David S. Fernández, Isabel F. Marín-Royo, Gema López-Sánchez, Inmaculada Martín-Doncel, Elena Vega, Francisco M. Lazo, Pedro A. |
author_sort | Moura, David S. |
collection | PubMed |
description | Sox2 is a pluripotency transcription factor that as an oncogene can also regulate cell proliferation. Therefore, genes implicated in several different aspects of cell proliferation, such as the VRK1 chromatin-kinase, are candidates to be targets of Sox2. Sox 2 and VRK1 colocalize in nuclei of proliferating cells forming a stable complex. Sox2 knockdown abrogates VRK1 gene expression. Depletion of either Sox2 or VRK1 caused a reduction of cell proliferation. Sox2 up-regulates VRK1 expression and both proteins cooperate in the activation of CCND1. The accumulation of VRK1 protein downregulates SOX2 expression and both proteins are lost in terminally differentiated cells. Induction of neural differentiation with retinoic acid resulted in downregulation of Sox2 and VRK1 that inversely correlated with the expression of differentiation markers such as N-cadherin, Pax6, mH2A1.2 and mH2A2. Differentiation-associated macro histones mH2A1.2and mH2A2 inhibit CCND1 and VRK1 expression and also block the activation of the VRK1 promoter by Sox2. VRK1 is a downstream target of Sox2 and both form an autoregulatory loop in epithelial cell differentiation. |
format | Online Article Text |
id | pubmed-4917848 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49178482016-06-27 Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation Moura, David S. Fernández, Isabel F. Marín-Royo, Gema López-Sánchez, Inmaculada Martín-Doncel, Elena Vega, Francisco M. Lazo, Pedro A. Sci Rep Article Sox2 is a pluripotency transcription factor that as an oncogene can also regulate cell proliferation. Therefore, genes implicated in several different aspects of cell proliferation, such as the VRK1 chromatin-kinase, are candidates to be targets of Sox2. Sox 2 and VRK1 colocalize in nuclei of proliferating cells forming a stable complex. Sox2 knockdown abrogates VRK1 gene expression. Depletion of either Sox2 or VRK1 caused a reduction of cell proliferation. Sox2 up-regulates VRK1 expression and both proteins cooperate in the activation of CCND1. The accumulation of VRK1 protein downregulates SOX2 expression and both proteins are lost in terminally differentiated cells. Induction of neural differentiation with retinoic acid resulted in downregulation of Sox2 and VRK1 that inversely correlated with the expression of differentiation markers such as N-cadherin, Pax6, mH2A1.2 and mH2A2. Differentiation-associated macro histones mH2A1.2and mH2A2 inhibit CCND1 and VRK1 expression and also block the activation of the VRK1 promoter by Sox2. VRK1 is a downstream target of Sox2 and both form an autoregulatory loop in epithelial cell differentiation. Nature Publishing Group 2016-06-23 /pmc/articles/PMC4917848/ /pubmed/27334688 http://dx.doi.org/10.1038/srep28532 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Moura, David S. Fernández, Isabel F. Marín-Royo, Gema López-Sánchez, Inmaculada Martín-Doncel, Elena Vega, Francisco M. Lazo, Pedro A. Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation |
title | Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation |
title_full | Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation |
title_fullStr | Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation |
title_full_unstemmed | Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation |
title_short | Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation |
title_sort | oncogenic sox2 regulates and cooperates with vrk1 in cell cycle progression and differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917848/ https://www.ncbi.nlm.nih.gov/pubmed/27334688 http://dx.doi.org/10.1038/srep28532 |
work_keys_str_mv | AT mouradavids oncogenicsox2regulatesandcooperateswithvrk1incellcycleprogressionanddifferentiation AT fernandezisabelf oncogenicsox2regulatesandcooperateswithvrk1incellcycleprogressionanddifferentiation AT marinroyogema oncogenicsox2regulatesandcooperateswithvrk1incellcycleprogressionanddifferentiation AT lopezsanchezinmaculada oncogenicsox2regulatesandcooperateswithvrk1incellcycleprogressionanddifferentiation AT martindoncelelena oncogenicsox2regulatesandcooperateswithvrk1incellcycleprogressionanddifferentiation AT vegafranciscom oncogenicsox2regulatesandcooperateswithvrk1incellcycleprogressionanddifferentiation AT lazopedroa oncogenicsox2regulatesandcooperateswithvrk1incellcycleprogressionanddifferentiation |