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Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis
The tumor suppressor retinoblastoma protein (pRb) is inactivated in a wide variety of cancers. While its role during cell cycle is well characterized, little is known about its properties on apoptosis regulation and apoptosis-induced cell responses. pRb shorter forms that can modulate pRB apoptotic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121136/ https://www.ncbi.nlm.nih.gov/pubmed/25089524 http://dx.doi.org/10.1371/journal.pone.0102902 |
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author | Milet, Cécile Rincheval-Arnold, Aurore Moriéras, Angéline Clavier, Amandine Garrigue, Alexandrine Mignotte, Bernard Guénal, Isabelle |
author_facet | Milet, Cécile Rincheval-Arnold, Aurore Moriéras, Angéline Clavier, Amandine Garrigue, Alexandrine Mignotte, Bernard Guénal, Isabelle |
author_sort | Milet, Cécile |
collection | PubMed |
description | The tumor suppressor retinoblastoma protein (pRb) is inactivated in a wide variety of cancers. While its role during cell cycle is well characterized, little is known about its properties on apoptosis regulation and apoptosis-induced cell responses. pRb shorter forms that can modulate pRB apoptotic properties, resulting from cleavages at caspase specific sites are observed in several cellular contexts. A bioinformatics analysis showed that a putative caspase cleavage site (TELD) is found in the Drosophila homologue of pRb (RBF) at a position similar to the site generating the p76Rb form in mammals. Thus, we generated a punctual mutant form of RBF in which the aspartate of the TELD site is replaced by an alanine. This mutant form, RBF(D253A), conserved the JNK-dependent pro-apoptotic properties of RBF but gained the ability of inducing overgrowth phenotypes in adult wings. We show that this overgrowth is a consequence of an abnormal proliferation in wing imaginal discs, which depends on the JNK pathway activation but not on wingless (wg) ectopic expression. These results show for the first time that the TELD site of RBF could be important to control the function of RBF in tissue homeostasis in vivo. |
format | Online Article Text |
id | pubmed-4121136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41211362014-08-05 Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis Milet, Cécile Rincheval-Arnold, Aurore Moriéras, Angéline Clavier, Amandine Garrigue, Alexandrine Mignotte, Bernard Guénal, Isabelle PLoS One Research Article The tumor suppressor retinoblastoma protein (pRb) is inactivated in a wide variety of cancers. While its role during cell cycle is well characterized, little is known about its properties on apoptosis regulation and apoptosis-induced cell responses. pRb shorter forms that can modulate pRB apoptotic properties, resulting from cleavages at caspase specific sites are observed in several cellular contexts. A bioinformatics analysis showed that a putative caspase cleavage site (TELD) is found in the Drosophila homologue of pRb (RBF) at a position similar to the site generating the p76Rb form in mammals. Thus, we generated a punctual mutant form of RBF in which the aspartate of the TELD site is replaced by an alanine. This mutant form, RBF(D253A), conserved the JNK-dependent pro-apoptotic properties of RBF but gained the ability of inducing overgrowth phenotypes in adult wings. We show that this overgrowth is a consequence of an abnormal proliferation in wing imaginal discs, which depends on the JNK pathway activation but not on wingless (wg) ectopic expression. These results show for the first time that the TELD site of RBF could be important to control the function of RBF in tissue homeostasis in vivo. Public Library of Science 2014-08-04 /pmc/articles/PMC4121136/ /pubmed/25089524 http://dx.doi.org/10.1371/journal.pone.0102902 Text en © 2014 Milet 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 Milet, Cécile Rincheval-Arnold, Aurore Moriéras, Angéline Clavier, Amandine Garrigue, Alexandrine Mignotte, Bernard Guénal, Isabelle Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis |
title | Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis |
title_full | Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis |
title_fullStr | Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis |
title_full_unstemmed | Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis |
title_short | Mutating RBF Can Enhance Its Pro-Apoptotic Activity and Uncovers a New Role in Tissue Homeostasis |
title_sort | mutating rbf can enhance its pro-apoptotic activity and uncovers a new role in tissue homeostasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121136/ https://www.ncbi.nlm.nih.gov/pubmed/25089524 http://dx.doi.org/10.1371/journal.pone.0102902 |
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