CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice

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CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice

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dc.contributor.author Ventelä, Sami
dc.contributor.author Côme, Christophe
dc.contributor.author Mäkelä, Juho-Antti
dc.contributor.author Mannermaa, Leni
dc.contributor.author Kallajoki, Markku
dc.contributor.author Chan, Edward K.
dc.contributor.author Toppari, Jorma
dc.contributor.author Westermarck, Jukka
dc.contributor.author Hobbs, Robin M.
dc.contributor.author Pandolfi, Pier Paolo
dc.date.accessioned 2013-02-20T19:38:56Z
dc.date.issued 2012
dc.identifier.citation Ventelä, Sami, Christophe Côme, Juho-Antti Mäkelä, Robin M. Hobbs, Leni Mannermaa, Markku Kallajoki, Edward K. Chan, Pier Paolo Pandolfi, Jorma Toppari, and Jukka Westermarck. 2012. CIP2A promotes proliferation of spermatogonial progenitor cells and spermatogenesis in mice. PLoS ONE 7(3): e33209. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:10318215
dc.description.abstract 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. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0033209 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312892/pdf/ en_US
dash.license LAA
dc.subject biology en_US
dc.subject anatomy en_US
dc.subject physiology en_US
dc.subject reproductive system en_US
dc.subject developmental biology en_US
dc.subject stem cells en_US
dc.subject model organisms en_US
dc.subject animal models en_US
dc.subject medicine en_US
dc.title CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Pandolfi, Pier Paolo
dc.date.available 2013-02-20T19:38:56Z

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