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Publication : Retinoblastoma protein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells.

First Author  Rotgers E Year  2014
Journal  Cell Death Dis Volume  5
Pages  e1274 PubMed ID  24901045
Mgi Jnum  J:267321 Mgi Id  MGI:6258833
Doi  10.1038/cddis.2014.232 Citation  Rotgers E, et al. (2014) Retinoblastoma protein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells. Cell Death Dis 5:e1274
abstractText  The retinoblastoma protein (RB) is essential for normal cell cycle control. RB function depends, at least in part, on interactions with the E2F family of DNA-binding transcription factors (E2Fs). To study the role of RB in the adult testis, a Sertoli cell (SC)-specific Rb knockout mouse line (SC-RbKO) was generated using the Cre/loxP recombination system. SC-RbKO mice exhibited an age-dependent testicular atrophy, impaired fertility, severe SC dysfunction, and spermatogenic defects. Removal of Rb in SC induced aberrant SC cycling, dedifferentiation, and apoptosis. Here we show that E2F3 is the only E2F expressed in mouse SCs and that RB interacts with E2F3 during mouse testicular development. In the absence of RB, the other retinoblastoma family members p107 and p130 began interacting with E2F3 in the adult testes. In vivo silencing of E2F3 partially restored the SC maturation and survival as well as spermatogenesis in the SC-RbKO mice. These results point to RB as a key regulator of SC function in adult mice and that the RB/E2F3 pathway directs SC maturation, cell cycle quiescence, and RB protects SC from apoptosis.
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