{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:31:56Z","timestamp":1789201916572,"version":"build-2803163510"},"reference-count":44,"publisher":"The Company of Biologists","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,2,15]]},"abstract":"<jats:p>Stil (Sil, SCL\/TAL1 interrupting locus) is a cytosolic and centrosomal protein expressed in proliferating cells that is required for mouse and zebrafish neural development and is mutated in familial microcephaly. Recently the Drosophila melanogaster ortholog of Stil was found to be important for centriole duplication. Consistent with this finding, we report here that mouse embryonic fibroblasts lacking Stil are characterized by slow growth, low mitotic index and absence of clear centrosomes. We hypothesized that Stil regulates mitosis through the tumor suppressor Chfr, an E3 ligase that blocks mitotic entry in response to mitotic stress. Mouse fibroblasts lacking Stil by genomic or RNA interference approaches, as well as E9.5 Stil\u2212\/\u2212 embryos, express high levels of the Chfr protein and reduced levels of the Chfr substrate Plk1. Exogenous expression of Stil, knockdown of Chfr or overexpression of Plk1 reverse the abnormal mitotic phenotypes of fibroblasts lacking Stil. We further demonstrate that Stil increases Chfr auto-ubiquitination and reduces its protein stability. Thus, Stil is required for centrosome organization, entry into mitosis and cell proliferation, and these functions are at least partially mediated by Chfr and its targets. This is the first identification of a negative regulator of the Chfr mitotic checkpoint.<\/jats:p>","DOI":"10.1242\/jcs.079731","type":"journal-article","created":{"date-parts":[[2011,1,19]],"date-time":"2011-01-19T04:49:44Z","timestamp":1295412584000},"page":"532-539","source":"Crossref","is-referenced-by-count":42,"title":["The Stil protein regulates centrosome integrity and mitosis through suppression of Chfr"],"prefix":"10.1242","volume":"124","author":[{"given":"Asher","family":"Castiel","sequence":"first","affiliation":[{"name":"Sheba Cancer Research Center and the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Ramat Gan, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal Mark","family":"Danieli","sequence":"additional","affiliation":[{"name":"Sheba Cancer Research Center and the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Ramat Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahuvit","family":"David","sequence":"additional","affiliation":[{"name":"Sheba Cancer Research Center and the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Ramat Gan, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Moshkovitz","sequence":"additional","affiliation":[{"name":"Sheba Cancer Research Center and the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Ramat Gan, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Aplan","sequence":"additional","affiliation":[{"name":"Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20889-5105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan R.","family":"Kirsch","sequence":"additional","affiliation":[{"name":"Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20889-5105, USA"},{"name":"Current address: Amgen Incorporated, Oncology Research, Amgen, 1201 Amgen Court West, AW1-J 4144, Seattle, WA 98119-3105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brandeis","sequence":"additional","affiliation":[{"name":"The Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Ram Hill, Jerusalem 91904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Molecular Hematology\/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Grabengasse, Heidelberg 69120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai","family":"Izraeli","sequence":"additional","affiliation":[{"name":"Sheba Cancer Research Center and the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Ramat Gan, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042520404196100_R1","doi-asserted-by":"crossref","first-page":"5462","DOI":"10.1128\/MCB.11.11.5462","article-title":"Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia","volume":"11","author":"Aplan","year":"1991","journal-title":"Mol. 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