| First Author | Creff J | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 6 | Pages | 112659 |
| PubMed ID | 37327110 | Mgi Jnum | J:337926 |
| Mgi Id | MGI:7508961 | Doi | 10.1016/j.celrep.2023.112659 |
| Citation | Creff J, et al. (2023) p57(Kip2) acts as a transcriptional corepressor to regulate intestinal stem cell fate and proliferation. Cell Rep 42(6):112659 |
| abstractText | p57(Kip2) is a cyclin/CDK inhibitor and a negative regulator of cell proliferation. Here, we report that p57 regulates intestinal stem cell (ISC) fate and proliferation in a CDK-independent manner during intestinal development. In the absence of p57, intestinal crypts exhibit an increased proliferation and an amplification of transit-amplifying cells and of Hopx(+) ISCs, which are no longer quiescent, while Lgr5(+) ISCs are unaffected. RNA sequencing (RNA-seq) analyses of Hopx(+) ISCs show major gene expression changes in the absence of p57. We found that p57 binds to and inhibits the activity of Ascl2, a transcription factor critical for ISC specification and maintenance, by participating in the recruitment of a corepressor complex to Ascl2 target gene promoters. Thus, our data suggest that, during intestinal development, p57 plays a key role in maintaining Hopx(+) ISC quiescence and repressing the ISC phenotype outside of the crypt bottom by inhibiting the transcription factor Ascl2 in a CDK-independent manner. |
