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Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death
The transcription factor Krox-20 controls Schwann cell myelination. Schwann cells in Krox-20 null mice fail to myelinate, and unlike myelinating Schwann cells, continue to proliferate and are susceptible to death. We find that enforced Krox-20 expression in Schwann cells cell-autonomously inactivate...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172235/ https://www.ncbi.nlm.nih.gov/pubmed/14757751 http://dx.doi.org/10.1083/jcb.200307132 |
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author | Parkinson, David B. Bhaskaran, Ambily Droggiti, Anna Dickinson, Sarah D'Antonio, Maurizio Mirsky, Rhona Jessen, Kristjan R. |
author_facet | Parkinson, David B. Bhaskaran, Ambily Droggiti, Anna Dickinson, Sarah D'Antonio, Maurizio Mirsky, Rhona Jessen, Kristjan R. |
author_sort | Parkinson, David B. |
collection | PubMed |
description | The transcription factor Krox-20 controls Schwann cell myelination. Schwann cells in Krox-20 null mice fail to myelinate, and unlike myelinating Schwann cells, continue to proliferate and are susceptible to death. We find that enforced Krox-20 expression in Schwann cells cell-autonomously inactivates the proliferative response of Schwann cells to the major axonal mitogen β–neuregulin-1 and the death response to TGFβ or serum deprivation. Even in 3T3 fibroblasts, Krox-20 not only blocks proliferation and death but also activates the myelin genes periaxin and protein zero, showing properties in common with master regulatory genes in other cell types. Significantly, a major function of Krox-20 is to suppress the c-Jun NH(2)-terminal protein kinase (JNK)–c-Jun pathway, activation of which is required for both proliferation and death. Thus, Krox-20 can coordinately control suppression of mitogenic and death responses. Krox-20 also up-regulates the scaffold protein JNK-interacting protein 1 (JIP-1). We propose this as a possible component of the mechanism by which Krox-20 regulates JNK activity during Schwann cell development. |
format | Text |
id | pubmed-2172235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21722352008-03-05 Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death Parkinson, David B. Bhaskaran, Ambily Droggiti, Anna Dickinson, Sarah D'Antonio, Maurizio Mirsky, Rhona Jessen, Kristjan R. J Cell Biol Article The transcription factor Krox-20 controls Schwann cell myelination. Schwann cells in Krox-20 null mice fail to myelinate, and unlike myelinating Schwann cells, continue to proliferate and are susceptible to death. We find that enforced Krox-20 expression in Schwann cells cell-autonomously inactivates the proliferative response of Schwann cells to the major axonal mitogen β–neuregulin-1 and the death response to TGFβ or serum deprivation. Even in 3T3 fibroblasts, Krox-20 not only blocks proliferation and death but also activates the myelin genes periaxin and protein zero, showing properties in common with master regulatory genes in other cell types. Significantly, a major function of Krox-20 is to suppress the c-Jun NH(2)-terminal protein kinase (JNK)–c-Jun pathway, activation of which is required for both proliferation and death. Thus, Krox-20 can coordinately control suppression of mitogenic and death responses. Krox-20 also up-regulates the scaffold protein JNK-interacting protein 1 (JIP-1). We propose this as a possible component of the mechanism by which Krox-20 regulates JNK activity during Schwann cell development. The Rockefeller University Press 2004-02-02 /pmc/articles/PMC2172235/ /pubmed/14757751 http://dx.doi.org/10.1083/jcb.200307132 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Parkinson, David B. Bhaskaran, Ambily Droggiti, Anna Dickinson, Sarah D'Antonio, Maurizio Mirsky, Rhona Jessen, Kristjan R. Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death |
title | Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death |
title_full | Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death |
title_fullStr | Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death |
title_full_unstemmed | Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death |
title_short | Krox-20 inhibits Jun-NH(2)-terminal kinase/c-Jun to control Schwann cell proliferation and death |
title_sort | krox-20 inhibits jun-nh(2)-terminal kinase/c-jun to control schwann cell proliferation and death |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172235/ https://www.ncbi.nlm.nih.gov/pubmed/14757751 http://dx.doi.org/10.1083/jcb.200307132 |
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