Show simple item record

dc.contributor.authorVentelä, Sami
dc.contributor.authorCôme, Christophe
dc.contributor.authorMäkelä, Juho-Antti
dc.contributor.authorHobbs, Robin M.
dc.contributor.authorMannermaa, Leni
dc.contributor.authorKallajoki, Markku
dc.contributor.authorChan, Edward K.
dc.contributor.authorPandolfi, Pier Paolo
dc.contributor.authorToppari, Jorma
dc.contributor.authorWestermarck, Jukka
dc.date.accessioned2013-02-20T19:38:56Z
dc.date.issued2012
dc.identifier.citationVentelä, 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.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10318215
dc.description.abstractProtein 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.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0033209en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312892/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectanatomyen_US
dc.subjectphysiologyen_US
dc.subjectreproductive systemen_US
dc.subjectdevelopmental biologyen_US
dc.subjectstem cellsen_US
dc.subjectmodel organismsen_US
dc.subjectanimal modelsen_US
dc.subjectmedicineen_US
dc.titleCIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorPandolfi, Pier Paolo
dc.date.available2013-02-20T19:38:56Z
dc.identifier.doi10.1371/journal.pone.0033209*
dash.contributor.affiliatedPandolfi, Pier Paolo


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record