| First Author | Nakagawa T | Year | 2017 |
| Journal | Development | Volume | 144 |
| Issue | 22 | Pages | 4137-4147 |
| PubMed ID | 28982686 | Mgi Jnum | J:248184 |
| Mgi Id | MGI:5926979 | Doi | 10.1242/dev.158485 |
| Citation | Nakagawa T, et al. (2017) Regulation of mitosis-meiosis transition by the ubiquitin ligase beta-TrCP in male germ cells. Development 144(22):4137-4147 |
| abstractText | The mitosis-meiosis transition is essential for spermatogenesis. Specific and timely downregulation of the transcription factor DMRT1, and consequent induction of Stra8 expression, is required for this process in mammals, but the molecular mechanism has remained unclear. Here, we show that beta-TrCP, the substrate recognition component of an E3 ubiquitin ligase complex, targets DMRT1 for degradation and thereby controls the mitosis-meiosis transition in mouse male germ cells. Conditional inactivation of beta-TrCP2 in male germ cells of beta-TrCP1 knockout mice resulted in sterility due to a lack of mature sperm. The beta-TrCP-deficient male germ cells did not enter meiosis, but instead underwent apoptosis. The induction of Stra8 expression was also attenuated in association with the accumulation of DMRT1 at the Stra8 promoter in beta-TrCP-deficient testes. DMRT1 contains a consensus beta-TrCP degron sequence that was found to bind beta-TrCP. Overexpression of beta-TrCP induced the ubiquitylation and degradation of DMRT1. Heterozygous deletion of Dmrt1 in beta-TrCP-deficient spermatogonia increased meiotic cells with a concomitant reduction of apoptosis. Collectively, our data indicate that beta-TrCP regulates the transition from mitosis to meiosis in male germ cells by targeting DMRT1 for degradation. |
