Abstract
Suppressor genetics in C. elegans has identified key components of the LIN-12/Notch signaling pathway. Here, we describe a genetic and molecular characterization of the suppressor gene sel-7. We show that reducing or eliminating sel-7 activity suppresses the effects of constitutive lin-12 activity, enhances the effects of partially reduced lin-12 activity, and causes a synthetic Lin-12(0) phenotype when combined with a null mutation in the sel-12 presenilin gene. These observations suggest that sel-7 is a positive regulator of lin-12 activity. We also show that SEL-7 encodes a novel nuclear protein. Through yeast two-hybrid screening, we identified an apparent interaction partner, K08E3.8, that also interacts with SEL-8, a known component of the nuclear complex that forms upon LIN-12 activation. Our data suggest potential roles for SEL-7 in the assembly or function of this nuclear complex.
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- Ailion M., Thomas J. H. Dauer formation induced by high temperatures in Caenorhabditis elegans. Genetics. 2000 Nov;156(3):1047–1067. doi: 10.1093/genetics/156.3.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Strooper B., Annaert W., Cupers P., Saftig P., Craessaerts K., Mumm J. S., Schroeter E. H., Schrijvers V., Wolfe M. S., Ray W. J. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999 Apr 8;398(6727):518–522. doi: 10.1038/19083. [DOI] [PubMed] [Google Scholar]
- Doyle T. G., Wen C., Greenwald I. SEL-8, a nuclear protein required for LIN-12 and GLP-1 signaling in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7877–7881. doi: 10.1073/pnas.97.14.7877. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fares H., Greenwald I. Genetic analysis of endocytosis in Caenorhabditis elegans: coelomocyte uptake defective mutants. Genetics. 2001 Sep;159(1):133–145. doi: 10.1093/genetics/159.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fares H., Greenwald I. SEL-5, a serine/threonine kinase that facilitates lin-12 activity in Caenorhabditis elegans. Genetics. 1999 Dec;153(4):1641–1654. doi: 10.1093/genetics/153.4.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenwald I. S., Sternberg P. W., Horvitz H. R. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell. 1983 Sep;34(2):435–444. doi: 10.1016/0092-8674(83)90377-x. [DOI] [PubMed] [Google Scholar]
- Greenwald I. LIN-12/Notch signaling: lessons from worms and flies. Genes Dev. 1998 Jun 15;12(12):1751–1762. doi: 10.1101/gad.12.12.1751. [DOI] [PubMed] [Google Scholar]
- Greenwald I., Seydoux G. Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans. Nature. 1990 Jul 12;346(6280):197–199. doi: 10.1038/346197a0. [DOI] [PubMed] [Google Scholar]
- Hodgkin J., Papp A., Pulak R., Ambros V., Anderson P. A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics. 1989 Oct;123(2):301–313. doi: 10.1093/genetics/123.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kitagawa M., Oyama T., Kawashima T., Yedvobnick B., Kumar A., Matsuno K., Harigaya K. A human protein with sequence similarity to Drosophila mastermind coordinates the nuclear form of notch and a CSL protein to build a transcriptional activator complex on target promoters. Mol Cell Biol. 2001 Jul;21(13):4337–4346. doi: 10.1128/MCB.21.13.4337-4346.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levitan D., Greenwald I. Effects of SEL-12 presenilin on LIN-12 localization and function in Caenorhabditis elegans. Development. 1998 Sep;125(18):3599–3606. doi: 10.1242/dev.125.18.3599. [DOI] [PubMed] [Google Scholar]
- Levitan D., Greenwald I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature. 1995 Sep 28;377(6547):351–354. doi: 10.1038/377351a0. [DOI] [PubMed] [Google Scholar]
- Mello C., Fire A. DNA transformation. Methods Cell Biol. 1995;48:451–482. [PubMed] [Google Scholar]
- Pepper Anita S-R, Killian Darrell J., Hubbard E. Jane Albert. Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition. Genetics. 2003 Jan;163(1):115–132. doi: 10.1093/genetics/163.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Petcherski A. G., Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature. 2000 May 18;405(6784):364–368. doi: 10.1038/35012645. [DOI] [PubMed] [Google Scholar]
- Petcherski A. G., Kimble J. Mastermind is a putative activator for Notch. Curr Biol. 2000 Jun 29;10(13):R471–R473. doi: 10.1016/s0960-9822(00)00577-7. [DOI] [PubMed] [Google Scholar]
- Pettitt J., Wood W. B., Plasterk R. H. cdh-3, a gene encoding a member of the cadherin superfamily, functions in epithelial cell morphogenesis in Caenorhabditis elegans. Development. 1996 Dec;122(12):4149–4157. doi: 10.1242/dev.122.12.4149. [DOI] [PubMed] [Google Scholar]
- Priess J. R., Schnabel H., Schnabel R. The glp-1 locus and cellular interactions in early C. elegans embryos. Cell. 1987 Nov 20;51(4):601–611. doi: 10.1016/0092-8674(87)90129-2. [DOI] [PubMed] [Google Scholar]
- Struhl G., Fitzgerald K., Greenwald I. Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell. 1993 Jul 30;74(2):331–345. doi: 10.1016/0092-8674(93)90424-o. [DOI] [PubMed] [Google Scholar]
- Struhl G., Greenwald I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature. 1999 Apr 8;398(6727):522–525. doi: 10.1038/19091. [DOI] [PubMed] [Google Scholar]
- Tax F. E., Thomas J. H., Ferguson E. L., Horvitz H. R. Identification and characterization of genes that interact with lin-12 in Caenorhabditis elegans. Genetics. 1997 Dec;147(4):1675–1695. doi: 10.1093/genetics/147.4.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Timmons L., Court D. L., Fire A. Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene. 2001 Jan 24;263(1-2):103–112. doi: 10.1016/s0378-1119(00)00579-5. [DOI] [PubMed] [Google Scholar]
- Timmons L., Fire A. Specific interference by ingested dsRNA. Nature. 1998 Oct 29;395(6705):854–854. doi: 10.1038/27579. [DOI] [PubMed] [Google Scholar]
- Weinmaster G. Notch signal transduction: a real rip and more. Curr Opin Genet Dev. 2000 Aug;10(4):363–369. doi: 10.1016/s0959-437x(00)00097-6. [DOI] [PubMed] [Google Scholar]
- Wen C., Metzstein M. M., Greenwald I. SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling. Development. 1997 Dec;124(23):4759–4767. doi: 10.1242/dev.124.23.4759. [DOI] [PubMed] [Google Scholar]
- Wu L., Aster J. C., Blacklow S. C., Lake R., Artavanis-Tsakonas S., Griffin J. D. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet. 2000 Dec;26(4):484–489. doi: 10.1038/82644. [DOI] [PubMed] [Google Scholar]
- Zhou S., Fujimuro M., Hsieh J. J., Chen L., Hayward S. D. A role for SKIP in EBNA2 activation of CBF1-repressed promoters. J Virol. 2000 Feb;74(4):1939–1947. doi: 10.1128/jvi.74.4.1939-1947.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]