Cytosolic sequestration of Prep1 influences early stages of T cell development.
<h4>Objective</h4>Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate...
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| Language: | English |
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Public Library of Science (PLoS)
2008-06-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0002424&type=printable |
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| author | Dmitry Penkov Martina Palazzolo Anna Mondino Francesco Blasi |
| author_facet | Dmitry Penkov Martina Palazzolo Anna Mondino Francesco Blasi |
| author_sort | Dmitry Penkov |
| collection | DOAJ |
| description | <h4>Objective</h4>Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the N-terminal fragment of Pbx1 (Pbx1NT) under the control of the Lck proximal promoter.<h4>Principal findings</h4>Pbx1NT causes Prep1 cytosolic sequestration, abolishes Prep1-dependent DNA-binding activity and results in reduced Pbx2 expression in developing thymocytes. Transgenic thymi reveal increased numbers of CD4(-) CD8(-) CD44(-) (DN3 and DN4) thymocytes, due to a higher frequency of DN2 and DN4 Pbx1NT thymocytes in the S phase. Transgenic thymocytes however do not accumulate at later stages, as revealed by a normal representation of CD4/CD8 double positive and single positive thymocytes, due to a higher rate of apoptotic cell death of DN4 Pbx1NT thymocytes.<h4>Conclusion</h4>The results obtained by genetic (Prep1 hypomorphic) and functional (Pbx1NT transgenic) inactivation of Prep1 support nonredundant roles for this homeodomain protein during different stages of T cell development. |
| format | Article |
| id | doaj-art-a5f57a18c7e24908bee454bc5b807ce8 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-a5f57a18c7e24908bee454bc5b807ce82025-08-20T03:22:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-06-0136e242410.1371/journal.pone.0002424Cytosolic sequestration of Prep1 influences early stages of T cell development.Dmitry PenkovMartina PalazzoloAnna MondinoFrancesco Blasi<h4>Objective</h4>Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the N-terminal fragment of Pbx1 (Pbx1NT) under the control of the Lck proximal promoter.<h4>Principal findings</h4>Pbx1NT causes Prep1 cytosolic sequestration, abolishes Prep1-dependent DNA-binding activity and results in reduced Pbx2 expression in developing thymocytes. Transgenic thymi reveal increased numbers of CD4(-) CD8(-) CD44(-) (DN3 and DN4) thymocytes, due to a higher frequency of DN2 and DN4 Pbx1NT thymocytes in the S phase. Transgenic thymocytes however do not accumulate at later stages, as revealed by a normal representation of CD4/CD8 double positive and single positive thymocytes, due to a higher rate of apoptotic cell death of DN4 Pbx1NT thymocytes.<h4>Conclusion</h4>The results obtained by genetic (Prep1 hypomorphic) and functional (Pbx1NT transgenic) inactivation of Prep1 support nonredundant roles for this homeodomain protein during different stages of T cell development.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0002424&type=printable |
| spellingShingle | Dmitry Penkov Martina Palazzolo Anna Mondino Francesco Blasi Cytosolic sequestration of Prep1 influences early stages of T cell development. PLoS ONE |
| title | Cytosolic sequestration of Prep1 influences early stages of T cell development. |
| title_full | Cytosolic sequestration of Prep1 influences early stages of T cell development. |
| title_fullStr | Cytosolic sequestration of Prep1 influences early stages of T cell development. |
| title_full_unstemmed | Cytosolic sequestration of Prep1 influences early stages of T cell development. |
| title_short | Cytosolic sequestration of Prep1 influences early stages of T cell development. |
| title_sort | cytosolic sequestration of prep1 influences early stages of t cell development |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0002424&type=printable |
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