dc.contributor.author | Le, Minh T. N. | |
dc.contributor.author | Shyh-Chang, Ng | |
dc.contributor.author | Khaw, Swea Ling | |
dc.contributor.author | Chin, Lingzi | |
dc.contributor.author | Teh, Cathleen | |
dc.contributor.author | Tay, Junliang | |
dc.contributor.author | O'Day, Elizabeth M. | |
dc.contributor.author | Korzh, Vladimir | |
dc.contributor.author | Yang, Henry | |
dc.contributor.author | Lal, Ashish | |
dc.contributor.author | Lieberman, Judy | |
dc.contributor.author | Lim, Bing | |
dc.contributor.author | Lodish, Harvey F | |
dc.date.accessioned | 2012-02-10T19:38:54Z | |
dc.date.available | 2012-02-10T19:38:54Z | |
dc.date.issued | 2011-09 | |
dc.date.submitted | 2011-03 | |
dc.identifier.issn | 1553-7390 | |
dc.identifier.issn | 1553-7404 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/69088 | |
dc.description.abstract | MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA–target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis. | en_US |
dc.description.sponsorship | Singapore. Agency for Science, Technology and Research | en_US |
dc.description.sponsorship | L'Oréal Singapore (L'Oréal Singapore for Women in Science National Fellow) | en_US |
dc.description.sponsorship | Singapore-MIT Alliance (grant C-382-641-001-091) | en_US |
dc.description.sponsorship | United States. National Institutes of Health (grant R01 DK068348) | en_US |
dc.description.sponsorship | United States. National Institutes of Health | en_US |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.pgen.1002242 | en_US |
dc.rights | Creative Commons Attribution | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ | en_US |
dc.source | PLoS | en_US |
dc.title | Conserved Regulation of p53 Network Dosage by MicroRNA–125b Occurs through Evolving miRNA–Target Gene Pairs | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Le, Minh T. N. et al. “Conserved Regulation of P53 Network Dosage by MicroRNA–125b Occurs Through Evolving miRNA–Target Gene Pairs.” Ed. Michael T. McManus. PLoS Genetics 7.9 (2011): e1002242. Web. 10 Feb. 2012. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.approver | Lodish, Harvey F. | |
dc.contributor.mitauthor | Lodish, Harvey F. | |
dc.relation.journal | PLoS Genetics | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Le, Minh T. N.; Shyh-Chang, Ng; Khaw, Swea Ling; Chin, Lingzi; Teh, Cathleen; Tay, Junliang; O'Day, Elizabeth; Korzh, Vladimir; Yang, Henry; Lal, Ashish; Lieberman, Judy; Lodish, Harvey F.; Lim, Bing | en |
dc.identifier.orcid | https://orcid.org/0000-0002-7029-7415 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |