{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:57:49Z","timestamp":1790398669484,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM131746"],"award-info":[{"award-number":["R35 GM131746"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastructure Programs","award":["P40 OD010440"],"award-info":[{"award-number":["P40 OD010440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Caenorhabditis elegans E protein ortholog HLH-2 is required for the specification and function of the anchor cell, a unique, terminally differentiated somatic gonad cell that organizes uterine and vulval development. Initially, 4 cells\u20142 \u03b1 cells and their sisters, the \u03b2 cells\u2014have the potential to be the sole anchor cell. The \u03b2 cells rapidly lose anchor cell potential and invariably become ventral uterine precursor cells, while the 2 \u03b1 cells interact via LIN-12\/Notch to resolve which will be the anchor cell and which will become another ventral uterine precursor cell. HLH-2 protein stability is dynamically regulated in cells with anchor cell potential; initially present in all 4 cells, HLH-2 is degraded in presumptive ventral uterine precursor cells while remaining stable in the anchor cell. Here, we demonstrate that stability of HLH-2 protein is regulated by the activity of lin-12\/Notch in both \u03b1 and \u03b2 cells. Our analysis provides evidence that activation of LIN-12 promotes degradation of HLH-2 as part of a negative feedback loop during the anchor cell\/ventral uterine precursor cell decision by the \u03b1 cells, and that absence of lin-12 activity in \u03b2 cells increases HLH-2 stability and may account for their propensity to adopt the anchor cell fate in a lin-12 null background. We also performed an RNA interference screen of 232 ubiquitin-related genes and identified 7 genes that contribute to HLH-2 degradation in ventral uterine precursor cells; however, stabilizing HLH-2 by depleting ubiquitin ligases in a lin-12(+) background does not result in supernumerary anchor cells, suggesting that LIN-12 activation does not oppose hlh-2 activity solely by causing HLH-2 protein degradation. Finally, we provide evidence for lin-12-independent transcriptional regulation of hlh-2 in \u03b2 cells that correlates with known differences in POP-1\/TCF levels and anchor cell potential between \u03b1 and \u03b2 cells. Together, our results indicate that hlh-2 activity is regulated at multiple levels to restrict the anchor cell fate to a single cell.<\/jats:p>","DOI":"10.1093\/g3journal\/jkac028","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T21:17:11Z","timestamp":1644355031000},"source":"Crossref","is-referenced-by-count":9,"title":["Influences of HLH-2 stability on anchor cell fate specification during<i>Caenorhabditis elegans<\/i>gonadogenesis"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3279-4306","authenticated-orcid":false,"given":"Justin M","family":"Benavidez","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0304-3738","authenticated-orcid":false,"given":"Jee Hun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of 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