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CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice
Protein phosphatase 2A (PP2A) is a critical regulator of protein serine/threonine phosphorylation. However, the physiological and developmental roles of different PP2A complexes are very poorly understood. Here, we show that a newly characterized PP2A inhibitory protein CIP2A is co-expressed with ki...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312892/ https://www.ncbi.nlm.nih.gov/pubmed/22461891 http://dx.doi.org/10.1371/journal.pone.0033209 |
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author | Ventelä, Sami Côme, Christophe Mäkelä, Juho-Antti Hobbs, Robin M. Mannermaa, Leni Kallajoki, Markku Chan, Edward K. Pandolfi, Pier Paolo Toppari, Jorma Westermarck, Jukka |
author_facet | Ventelä, Sami Côme, Christophe Mäkelä, Juho-Antti Hobbs, Robin M. Mannermaa, Leni Kallajoki, Markku Chan, Edward K. Pandolfi, Pier Paolo Toppari, Jorma Westermarck, Jukka |
author_sort | Ventelä, Sami |
collection | PubMed |
description | Protein phosphatase 2A (PP2A) is a critical regulator of protein serine/threonine phosphorylation. However, the physiological and developmental roles of different PP2A complexes are very poorly understood. Here, we show that a newly characterized PP2A inhibitory protein CIP2A is co-expressed with ki-67 and with self-renewal protein PLZF in the spermatogonial progenitor cell (SPC) population in the testis. CIP2A and PLZF expression was shown also to correlate Ki-67 expression in human testicular spermatogonia. Functionally, CIP2A mutant mouse testes exhibited smaller number of PLZF-positive SPCs and reduced sperm counts. Moreover, seminiferous tubuli cells isolated from CIP2A mutant mice showed reduced expression of Plzf and other renewal genes Oct-4 and Nanog at mRNA level. However, PLZF-deficient testes did not show altered CIP2A expression. Importantly, spermatogonia-specific restoration of CIP2A expression rescued PLZF expression and sperm production defects observed in CIP2A mutant mice. Taken together, these results reveal first physiological function for an emerging human oncoprotein CIP2A, and provide insights into maintenance of PLZF-positive progenitors. Moreover, demonstration that CIP2A expression can be systematically inhibited without severe consequences to normal mouse development and viability may have clinical relevance regarding targeting of oncogenic CIP2A for future cancer therapies. |
format | Online Article Text |
id | pubmed-3312892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33128922012-03-29 CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice Ventelä, Sami Côme, Christophe Mäkelä, Juho-Antti Hobbs, Robin M. Mannermaa, Leni Kallajoki, Markku Chan, Edward K. Pandolfi, Pier Paolo Toppari, Jorma Westermarck, Jukka PLoS One Research Article Protein phosphatase 2A (PP2A) is a critical regulator of protein serine/threonine phosphorylation. However, the physiological and developmental roles of different PP2A complexes are very poorly understood. Here, we show that a newly characterized PP2A inhibitory protein CIP2A is co-expressed with ki-67 and with self-renewal protein PLZF in the spermatogonial progenitor cell (SPC) population in the testis. CIP2A and PLZF expression was shown also to correlate Ki-67 expression in human testicular spermatogonia. Functionally, CIP2A mutant mouse testes exhibited smaller number of PLZF-positive SPCs and reduced sperm counts. Moreover, seminiferous tubuli cells isolated from CIP2A mutant mice showed reduced expression of Plzf and other renewal genes Oct-4 and Nanog at mRNA level. However, PLZF-deficient testes did not show altered CIP2A expression. Importantly, spermatogonia-specific restoration of CIP2A expression rescued PLZF expression and sperm production defects observed in CIP2A mutant mice. Taken together, these results reveal first physiological function for an emerging human oncoprotein CIP2A, and provide insights into maintenance of PLZF-positive progenitors. Moreover, demonstration that CIP2A expression can be systematically inhibited without severe consequences to normal mouse development and viability may have clinical relevance regarding targeting of oncogenic CIP2A for future cancer therapies. Public Library of Science 2012-03-26 /pmc/articles/PMC3312892/ /pubmed/22461891 http://dx.doi.org/10.1371/journal.pone.0033209 Text en Ventelä 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 Ventelä, Sami Côme, Christophe Mäkelä, Juho-Antti Hobbs, Robin M. Mannermaa, Leni Kallajoki, Markku Chan, Edward K. Pandolfi, Pier Paolo Toppari, Jorma Westermarck, Jukka CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice |
title | CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice |
title_full | CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice |
title_fullStr | CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice |
title_full_unstemmed | CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice |
title_short | CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice |
title_sort | cip2a promotes proliferation of spermatogonial progenitor cells and spermatogenesis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312892/ https://www.ncbi.nlm.nih.gov/pubmed/22461891 http://dx.doi.org/10.1371/journal.pone.0033209 |
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