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14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization
The homozygous repeated epilation (Er/Er) mouse mutant of the gene encoding 14-3-3σ displays an epidermal phenotype characterized by hyperproliferative keratinocytes and undifferentiated epidermis. Heterozygous Er/+ mice develop spontaneous skin tumors and are highly sensitive to tumor-promoting DMB...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430425/ https://www.ncbi.nlm.nih.gov/pubmed/25668240 http://dx.doi.org/10.1038/jid.2015.42 |
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author | Sambandam, Sumitha A.T. Kasetti, Ramesh Babu Xue, Lei Dean, Douglas C. Lu, Qingxian Li, Qiutang |
author_facet | Sambandam, Sumitha A.T. Kasetti, Ramesh Babu Xue, Lei Dean, Douglas C. Lu, Qingxian Li, Qiutang |
author_sort | Sambandam, Sumitha A.T. |
collection | PubMed |
description | The homozygous repeated epilation (Er/Er) mouse mutant of the gene encoding 14-3-3σ displays an epidermal phenotype characterized by hyperproliferative keratinocytes and undifferentiated epidermis. Heterozygous Er/+ mice develop spontaneous skin tumors and are highly sensitive to tumor-promoting DMBA/TPA induction. The molecular mechanisms underlying 14-3-3σ regulation of epidermal proliferation, differentiation, and tumor formation have not been well elucidated. In the present study, we found that Er/Er keratinocytes failed to sequester Yap1 in the cytoplasm, leading to its nuclear localization during epidermal development in vivo and under differentiation-inducing culture conditions in vitro. In addition, enhanced Yap1 nuclear localization was also evident in DMBA/TPA-induced tumors from Er/+ skin. Furthermore, shRNA knockdown of Yap1 expression in Er/Er keratinocytes inhibited their proliferation, suggesting that YAP1 functions as a downstream effector of 14-3-3σ controlling epidermal proliferation. We then demonstrated that keratinocytes express all seven 14-3-3 protein isoforms, some of which form heterodimers with 14-3-3σ, either full-length WT or the mutant form found in Er/Er mice. However Er 14-3-3σ does not interact with Yap1, as demonstrated by co-immunoprecipitation. We conclude that Er 14-3-3σ disrupts the interaction between 14-3-3 and Yap1, thus fails to block Yap1 nuclear transcriptional function, causing continued progenitor expansion and inhibition of differentiation in Er/Er epidermis. |
format | Online Article Text |
id | pubmed-4430425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44304252015-12-01 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization Sambandam, Sumitha A.T. Kasetti, Ramesh Babu Xue, Lei Dean, Douglas C. Lu, Qingxian Li, Qiutang J Invest Dermatol Article The homozygous repeated epilation (Er/Er) mouse mutant of the gene encoding 14-3-3σ displays an epidermal phenotype characterized by hyperproliferative keratinocytes and undifferentiated epidermis. Heterozygous Er/+ mice develop spontaneous skin tumors and are highly sensitive to tumor-promoting DMBA/TPA induction. The molecular mechanisms underlying 14-3-3σ regulation of epidermal proliferation, differentiation, and tumor formation have not been well elucidated. In the present study, we found that Er/Er keratinocytes failed to sequester Yap1 in the cytoplasm, leading to its nuclear localization during epidermal development in vivo and under differentiation-inducing culture conditions in vitro. In addition, enhanced Yap1 nuclear localization was also evident in DMBA/TPA-induced tumors from Er/+ skin. Furthermore, shRNA knockdown of Yap1 expression in Er/Er keratinocytes inhibited their proliferation, suggesting that YAP1 functions as a downstream effector of 14-3-3σ controlling epidermal proliferation. We then demonstrated that keratinocytes express all seven 14-3-3 protein isoforms, some of which form heterodimers with 14-3-3σ, either full-length WT or the mutant form found in Er/Er mice. However Er 14-3-3σ does not interact with Yap1, as demonstrated by co-immunoprecipitation. We conclude that Er 14-3-3σ disrupts the interaction between 14-3-3 and Yap1, thus fails to block Yap1 nuclear transcriptional function, causing continued progenitor expansion and inhibition of differentiation in Er/Er epidermis. 2015-02-10 2015-06 /pmc/articles/PMC4430425/ /pubmed/25668240 http://dx.doi.org/10.1038/jid.2015.42 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Sambandam, Sumitha A.T. Kasetti, Ramesh Babu Xue, Lei Dean, Douglas C. Lu, Qingxian Li, Qiutang 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization |
title | 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization |
title_full | 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization |
title_fullStr | 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization |
title_full_unstemmed | 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization |
title_short | 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating Yap1 cellular localization |
title_sort | 14-3-3σ regulates keratinocyte proliferation and differentiation by modulating yap1 cellular localization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430425/ https://www.ncbi.nlm.nih.gov/pubmed/25668240 http://dx.doi.org/10.1038/jid.2015.42 |
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