3brd

Structural highlights

Function

LAG1_CAEEL Transcriptional regulator that plays a central role in lin-12/Notch and glp-1/Notch signaling pathways, involved in cell-cell communication that regulate a broad spectrum of cell-fate determinations (PubMed:8625826). Binds directly to the 5'-[A/G]TGGGAA-3' DNA consensus sequence, which is present in the regulatory region of several genes (PubMed:8625826, PubMed:18706403, PubMed:23615264, PubMed:15297877, PubMed:32196486, PubMed:21737278). Acts as a transcriptional repressor when it is not associated with Notch proteins (By similarity). When in a complex with a Notch intracellular domain (NICD) product of lin-12/Notch or glp-1/Notch, and transcription regulator lag-3, it may act as a transcriptional activator that activates transcription of target genes(PubMed:18381292, PubMed:10830967, PubMed:32196486, PubMed:9003776). Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively (By similarity). Autonomously required in the germline for the stem cell fate, acting in the glp-1-dependent transcriptional activation of genes, including lst-1 and sygl-1 (PubMed:32196486). Involved in cell-fate specification during reproductive system development, by positively autoregulating its own expression, in response to lin-12/Notch signaling (PubMed:23615264, PubMed:32839181). Plays a role in Notch-dependent induction of left-right asymmetry in interneurons and motoneurons (PubMed:21737278). May repress expression of hlh-6, in a lin-12/Notch-independent manner (PubMed:18706403).[UniProtKB:P28159]^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Petcherski AG, Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature. 2000 May 18;405(6784):364-8. PMID:10830967 doi:10.1038/35012645
2. ↑ Kovall RA, Hendrickson WA. Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA. EMBO J. 2004 Sep 1;23(17):3441-51. Epub 2004 Aug 5. PMID:15297877 doi:10.1038/sj.emboj.7600349
3. ↑ Friedmann DR, Wilson JJ, Kovall RA. RAM-induced allostery facilitates assembly of a notch pathway active transcription complex. J Biol Chem. 2008 May 23;283(21):14781-91. Epub 2008 Apr 1. PMID:18381292 doi:http://dx.doi.org/10.1074/jbc.M709501200
4. ↑ Ghai V, Gaudet J. The CSL transcription factor LAG-1 directly represses hlh-6 expression in C. elegans. Dev Biol. 2008 Oct 15;322(2):334-44. PMID:18706403 doi:10.1016/j.ydbio.2008.07.018
5. ↑ Bertrand V, Bisso P, Poole RJ, Hobert O. Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons. Curr Biol. 2011 Jul 26;21(14):1225-31. PMID:21737278 doi:10.1016/j.cub.2011.06.016
6. ↑ Choi VN, Park SK, Hwang BJ. Clustered LAG-1 binding sites in lag-1/CSL are involved in regulating lag-1 expression during lin-12/Notch-dependent cell-fate specification. BMB Rep. 2013 Apr;46(4):219-24. PMID:23615264 doi:10.5483/bmbrep.2013.46.4.269
7. ↑ Chen J, Mohammad A, Pazdernik N, Huang H, Bowman B, Tycksen E, Schedl T. GLP-1 Notch-LAG-1 CSL control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1. PLoS Genet. 2020 Mar 20;16(3):e1008650. PMID:32196486 doi:10.1371/journal.pgen.1008650
8. ↑ Luo KL, Underwood RS, Greenwald I. Positive autoregulation of lag-1 in response to LIN-12 activation in cell fate decisions during C. elegans reproductive system development. Development. 2020 Sep 28;147(18):dev193482. PMID:32839181 doi:10.1242/dev.193482
9. ↑ Christensen S, Kodoyianni V, Bosenberg M, Friedman L, Kimble J. lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). Development. 1996 May;122(5):1373-83. PMID:8625826 doi:10.1242/dev.122.5.1373