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CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice




TekijätVentela S, Come C, Makela JA, Hobbs RM, Mannermaa L, Kallajoki M, Chan EK, Pandolfi PP, Toppari J, Westermarck J

KustantajaPUBLIC LIBRARY SCIENCE

Julkaisuvuosi2012

JournalPLoS ONE

Tietokannassa oleva lehden nimiPLOS ONE

Lehden akronyymiPLOS ONE

Artikkelin numeroARTN e33209

Numero sarjassa3

Vuosikerta7

Numero3

Aloitussivue3329

Sivujen määrä10

ISSN1932-6203

DOIhttps://doi.org/10.1371/journal.pone.0033209


Tiivistelmä
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.



Last updated on 2024-26-11 at 18:36