{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:50:35Z","timestamp":1772751035134,"version":"3.50.1"},"reference-count":52,"publisher":"The Company of Biologists","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,3,1]]},"abstract":"<jats:p>The LIN-1 ETS transcription factor inhibits vulval cell fates during Caenorhabditis elegans development. We demonstrate that LIN-1 interacts with UBC-9, a small ubiquitin-related modifier (SUMO) conjugating enzyme. This interaction is mediated by two consensus sumoylation motifs in LIN-1. Biochemical studies showed that LIN-1 is covalently modified by SUMO-1. ubc-9 and smo-1, the gene encoding SUMO-1, inhibit vulval cell fates and function at the level of lin-1, indicating that sumoylation promotes LIN-1 inhibition of vulval cell fates. Sumoylation of LIN-1 promoted transcriptional repression and mediated an interaction with MEP-1, a protein previously shown to associate with the nucleosome remodeling and histone deacetylation (NuRD) transcriptional repression complex. Genetic studies showed that mep-1 inhibits vulval cell fates and functions at the level of lin-1. We propose that sumoylation of LIN-1 mediates an interaction with MEP-1 that contributes to transcriptional repression of genes that promote vulval cell fates. These studies identify a molecular mechanism for SUMO-mediated transcriptional repression.<\/jats:p>","DOI":"10.1242\/dev.01664","type":"journal-article","created":{"date-parts":[[2005,2,3]],"date-time":"2005-02-03T01:23:19Z","timestamp":1107393799000},"page":"1047-1056","source":"Crossref","is-referenced-by-count":53,"title":["Sumoylation of LIN-1 promotes transcriptional repression and inhibition of vulval cell fates"],"prefix":"10.1242","volume":"132","author":[{"given":"Elizabeth R.","family":"Leight","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Pharmacology Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Glossip","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Pharmacology Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"Kornfeld","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Pharmacology Washington University School of Medicine, St Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042605320351200_REF1","unstructured":"Bartel, P. L., Chien, C.-T., Sternglanz, R. and Fields, S.(1993). In Cellular Interactions in Development: A Practical Approach (ed. D. A. Hartley), p.153. Oxford: Oxford University Press."},{"key":"2021042605320351200_REF2","doi-asserted-by":"crossref","unstructured":"Beitel, G. J., Tuck, S., Greenwald, I. and Horvitz, H. R.(1995). The Caenorhabditis elegans gene lin-1encodes an ETS-domain protein and defines a branch of the vulval induction pathway. Genes Dev9,3149-3162.","DOI":"10.1101\/gad.9.24.3149"},{"key":"2021042605320351200_REF3","doi-asserted-by":"crossref","unstructured":"Belfiore, M., Mathies, L. D., Pugnale, P., Moulder, G.,Barstead, R., Kimble, J. and Puoti, A. (2002). The MEP-1 zinc-finger protein acts with MOG DEAH box proteins to control gene expression via the fem-3 3\u2032 untranslated region in Caenorhabditis elegans. RNA8,725-739.","DOI":"10.1017\/S1355838202028595"},{"key":"2021042605320351200_REF4","unstructured":"Belfiore, M., Pugnale, P., Saudan, Z. and Puoti, A.(2004). Roles of the C. elegans cyclophilin-like protein MOG-6 in MEP-1 binding and germline fates. Development131,2935-2945."},{"key":"2021042605320351200_REF5","doi-asserted-by":"crossref","unstructured":"Bies, J., Markus, J. and Wolff, L. (2002). Covalent attachment of the SUMO-1 protein to the negative regulatory domain of the c-Myb transcription factor modifies its stability and transactivation capacity. J. Biol. Chem.277,8999-9009.","DOI":"10.1074\/jbc.M110453200"},{"key":"2021042605320351200_REF6","doi-asserted-by":"crossref","unstructured":"Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics77, 71-94.","DOI":"10.1093\/genetics\/77.1.71"},{"key":"2021042605320351200_REF7","doi-asserted-by":"crossref","unstructured":"Broday, L., Kolotuev, I., Didier, C., Bhoumik, A., Gupta, B. P.,Sternberg, P. W., Podbilewicz, B. and Ronai, Z. (2004). The small ubiquitin-like modifier (SUMO) is required for gonadal and uterine-vulval morphogenesis in Caenorhabditis elegans. Genes Dev.18,2380-2391.","DOI":"10.1101\/gad.1227104"},{"key":"2021042605320351200_REF8","doi-asserted-by":"crossref","unstructured":"Dahle, O., Andersen, T. O., Nordgard, O., Matre, V., del Sal, G. and Gabrielsen, O. S. (2003). Transactivation properties of c-Myb are critically dependent on two SUMO-1 acceptor sites that are conjugated in a PIASy enhanced manner. Eur. J. Biochem.270,1338-1348.","DOI":"10.1046\/j.1432-1033.2003.03504.x"},{"key":"2021042605320351200_REF9","doi-asserted-by":"crossref","unstructured":"Desterro, J. M., Rodriguez, M. S., Kemp, G. D. and Hay, R. T. (1999). Identification of the enzyme required for activation of the small ubiquitin-like protein SUMO-1. J. Biol. Chem.274,10618-10624.","DOI":"10.1074\/jbc.274.15.10618"},{"key":"2021042605320351200_REF10","doi-asserted-by":"crossref","unstructured":"Desterro, J. M., Thomson, J. and Hay, R. T.(1997). Ubch9 conjugates SUMO but not ubiquitin. FEBS Lett.417,297-300.","DOI":"10.1016\/S0014-5793(97)01305-7"},{"key":"2021042605320351200_REF11","doi-asserted-by":"crossref","unstructured":"Fantz, D. A., Jacobs, D., Glossip, D. and Kornfeld, K.(2001). Docking sites on substrate proteins direct extracellular signal-regulated kinase to phosphorylate specific residues. J. Biol. Chem.276,27256-27265.","DOI":"10.1074\/jbc.M102512200"},{"key":"2021042605320351200_REF12","doi-asserted-by":"crossref","unstructured":"Ferguson, E. L., Sternberg, P. W. and Horvitz, H. R.(1987). A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature326,259-267.","DOI":"10.1038\/326259a0"},{"key":"2021042605320351200_REF13","unstructured":"Fraser, A. G., Kamath, R. S., Zipperlen, P., Martinez-Campos,M., Sohrmann, M. and Ahringer, J. (2000). Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature408,325-330."},{"key":"2021042605320351200_REF14","doi-asserted-by":"crossref","unstructured":"Gill, G. (2003). Post-translational modification by the small ubiquitin-related modifier SUMO has big effects on transcription factor activity. Curr. Opin. Genet Dev.13,108-113.","DOI":"10.1016\/S0959-437X(03)00021-2"},{"key":"2021042605320351200_REF15","doi-asserted-by":"crossref","unstructured":"Girdwood, D., Bumpass, D., Vaughan, O. A., Thain, A., Anderson,L. A., Snowden, A. W., Garcia-Wilson, E., Perkins, N. D. and Hay, R. T.(2003). P300 transcriptional repression is mediated by SUMO modification. Mol. Cell11,1043-1054.","DOI":"10.1016\/S1097-2765(03)00141-2"},{"key":"2021042605320351200_REF16","unstructured":"Greenwald, I. S. (1997). Development of the vulva. In C. elegans II (ed. D. L. Riddle, T. Blumenthal, B. J. Meyer and J. R. Preiss), pp.519-541. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press."},{"key":"2021042605320351200_REF17","doi-asserted-by":"crossref","unstructured":"Hong, Y., Rogers, R., Matunis, M. J., Mayhew, C. N., Goodson, M. L., Park-Sarge, O. K., Sarge, K. D. and Goodson, M. (2001). Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 modification. J. Biol. Chem.276,40263-40267.","DOI":"10.1074\/jbc.M104714200"},{"key":"2021042605320351200_REF18","doi-asserted-by":"crossref","unstructured":"Horvitz, H. R. and Sternberg, P. W. (1991). Multiple intercellular signalling systems control the development of the Caenorhabditis elegans vulva. Nature351,535-541.","DOI":"10.1038\/351535a0"},{"key":"2021042605320351200_REF19","doi-asserted-by":"crossref","unstructured":"Jacobs, D., Beitel, G. J., Clark, S. G., Horvitz, H. R. and Kornfeld, K. (1998). Gain-of-function mutations in the Caenorhabditis elegans lin-1 ETS gene identify a C-terminal regulatory domain phosphorylated by ERK MAP kinase. Genetics149,1809-1822.","DOI":"10.1093\/genetics\/149.4.1809"},{"key":"2021042605320351200_REF20","doi-asserted-by":"crossref","unstructured":"Jacobs, D., Glossip, D., Xing, H., Muslin, A. J. and Kornfeld,K. (1999). Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase. Genes Dev.13,163-175.","DOI":"10.1101\/gad.13.2.163"},{"key":"2021042605320351200_REF21","doi-asserted-by":"crossref","unstructured":"Johnson, E. S. and Blobel, G. (1997). Ubc9p is the conjugating enzyme for the ubiquitin-like protein Smt3p. J. Biol. Chem.272,26799-26802.","DOI":"10.1074\/jbc.272.43.26799"},{"key":"2021042605320351200_REF22","doi-asserted-by":"crossref","unstructured":"Johnson, E. S. and Blobel, G. (1999). Cell cycle-regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J. Cell Biol.147,981-994.","DOI":"10.1083\/jcb.147.5.981"},{"key":"2021042605320351200_REF23","doi-asserted-by":"crossref","unstructured":"Johnson, E. S., Schwienhorst, I., Dohmen, R. J. and Blobel,G. (1997). The ubiquitin-like protein Smt3p is activated for conjugation to other proteins by an Aos1p\/Uba2p heterodimer. EMBO J.16,5509-5519.","DOI":"10.1093\/emboj\/16.18.5509"},{"key":"2021042605320351200_REF24","doi-asserted-by":"crossref","unstructured":"Kamath, R. S., Fraser, A. G., Dong, Y., Poulin, G., Durbin, R.,Gotta, M., Kanapin, A., le Bot, N., Moreno, S., Sohrmann, M. et al.(2003). Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature421,231-237.","DOI":"10.1038\/nature01278"},{"key":"2021042605320351200_REF25","doi-asserted-by":"crossref","unstructured":"Kim, J., Cantwell, C. A., Johnson, P. F., Pfarr, C. M. and Williams, S. C. (2002). Transcriptional activity of CCAAT\/enhancer-binding proteins is controlled by a conserved inhibitory domain that is a target for sumoylation. J. Biol. Chem.277,38037-38044.","DOI":"10.1074\/jbc.M207235200"},{"key":"2021042605320351200_REF26","doi-asserted-by":"crossref","unstructured":"Kornfeld, K. (1997). Vulval development in Caenorhabditis elegans. Trends Genet.13, 55-61.","DOI":"10.1016\/S0168-9525(97)01005-6"},{"key":"2021042605320351200_REF27","doi-asserted-by":"crossref","unstructured":"Kornfeld, K., Guan, K. L. and Horvitz, H. R.(1995). The Caenorhabditis elegans gene mek-2is required for vulval induction and encodes a protein similar to the protein kinase MEK. Genes Dev.9, 756-768.","DOI":"10.1101\/gad.9.6.756"},{"key":"2021042605320351200_REF28","doi-asserted-by":"crossref","unstructured":"Lackner, M. R., Kornfeld, K., Miller, L. M., Horvitz, H. R. and Kim, S. K. (1994). A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans. Genes Dev.8, 160-173.","DOI":"10.1101\/gad.8.2.160"},{"key":"2021042605320351200_REF29","doi-asserted-by":"crossref","unstructured":"Lemercier, C., Verdel, A., Galloo, B., Curtet, S., Brocard, M. P. and Khochbin, S. (2000). mHDA1\/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity. J. Biol. Chem.275,15594-15599.","DOI":"10.1074\/jbc.M908437199"},{"key":"2021042605320351200_REF30","doi-asserted-by":"crossref","unstructured":"Lin, X., Sun, B., Liang, M., Liang, Y. Y., Gast, A., Hildebrand,J., Brunicardi, F. C., Melchior, F. and Feng, X. H. (2003). Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Mol. Cell11,1389-1396.","DOI":"10.1016\/S1097-2765(03)00175-8"},{"key":"2021042605320351200_REF31","doi-asserted-by":"crossref","unstructured":"Miley, G. R., Fantz, D., Glossip, D., Lu, X., Saito, R. M.,Palmer, R. E., Inoue, T., van den Heuvel, S., Sternberg, P. W. and Kornfeld,K. (2004). Identification of residues of the Caenorhabditis elegans LIN-1 ETS domain that are necessary for DNA binding and regulation of vulval cell fates. Genetics167,1697-1709.","DOI":"10.1534\/genetics.104.029017"},{"key":"2021042605320351200_REF32","doi-asserted-by":"crossref","unstructured":"Muller, S., Berger, M., Lehembre, F., Seeler, J. S., Haupt, Y. and Dejean, A. (2000). c-Jun and p53 activity is modulated by SUMO-1 modification. J. Biol. Chem.275,13321-13329.","DOI":"10.1074\/jbc.275.18.13321"},{"key":"2021042605320351200_REF33","doi-asserted-by":"crossref","unstructured":"Ross, S., Best, J. L., Zon, L. I. and Gill, G.(2002). SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization. Mol. Cell10,831-842.","DOI":"10.1016\/S1097-2765(02)00682-2"},{"key":"2021042605320351200_REF34","unstructured":"Sambrook, J., Fritsch, E. F. and Maniatis, T.(1989). Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press."},{"key":"2021042605320351200_REF35","doi-asserted-by":"crossref","unstructured":"Sampson, D. A., Wang, M. and Matunis, M. J.(2001). The small ubiquitin-like modifier-1 (SUMO-1) consensus sequence mediates Ubc9 binding and is essential for SUMO-1 modification. J. Biol. Chem.276,21664-21669.","DOI":"10.1074\/jbc.M100006200"},{"key":"2021042605320351200_REF36","doi-asserted-by":"crossref","unstructured":"Sapetschnig, A., Rischitor, G., Braun, H., Doll, A., Schergaut,M., Melchior, F. and Suske, G. (2002). Transcription factor Sp3 is silenced through SUMO modification by PIAS1. EMBO J.21,5206-5215.","DOI":"10.1093\/emboj\/cdf510"},{"key":"2021042605320351200_REF37","doi-asserted-by":"crossref","unstructured":"Schiestl, R. H. and Gietz, R. D. (1989). High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr. Genet.16,339-346.","DOI":"10.1007\/BF00340712"},{"key":"2021042605320351200_REF38","doi-asserted-by":"crossref","unstructured":"Schwarz, S. E., Matuschewski, K., Liakopoulos, D., Scheffner, M. and Jentsch, S. (1998). The ubiquitin-like proteins SMT3 and SUMO-1 are conjugated by the UBC9 E2 enzyme. Proc. Natl. Acad. Sci. USA95,560-564.","DOI":"10.1073\/pnas.95.2.560"},{"key":"2021042605320351200_REF39","doi-asserted-by":"crossref","unstructured":"Sternberg, P. W. and Han, M. (1998). Genetics of RAS signaling in C. elegans. Trends Genet.14,466-472.","DOI":"10.1016\/S0168-9525(98)01592-3"},{"key":"2021042605320351200_REF40","doi-asserted-by":"crossref","unstructured":"Subramanian, L., Benson, M. D. and Iniguez-Lluhi, J. A.(2003). A synergy control motif within the attenuator domain of CCAAT\/enhancer-binding protein alpha inhibits transcriptional synergy through its PIASy-enhanced modification by SUMO-1 or SUMO-3. J. Biol. Chem.278,9134-9141.","DOI":"10.1074\/jbc.M210440200"},{"key":"2021042605320351200_REF41","doi-asserted-by":"crossref","unstructured":"Tan, P. B., Lackner, M. R. and Kim, S. K.(1998). MAP kinase signaling specificity mediated by the LIN-1 Ets\/LIN-31 WH transcription factor complex during C. elegans vulval induction. Cell93,569-580.","DOI":"10.1016\/S0092-8674(00)81186-1"},{"key":"2021042605320351200_REF42","doi-asserted-by":"crossref","unstructured":"Timmons, L. and Fire, A. (1998). Specific interference by ingested dsRNA. Nature395, 854.","DOI":"10.1038\/27579"},{"key":"2021042605320351200_REF43","doi-asserted-by":"crossref","unstructured":"Tong, J. K., Hassig, C. A., Schnitzler, G. R., Kingston, R. E. and Schreiber, S. L. (1998). Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature395,917-921.","DOI":"10.1038\/27699"},{"key":"2021042605320351200_REF44","doi-asserted-by":"crossref","unstructured":"Treisman, R. (1994). Ternary complex factors:growth factor regulated transcriptional activators. Curr. Opin. Genet. Dev.4,96-101.","DOI":"10.1016\/0959-437X(94)90097-3"},{"key":"2021042605320351200_REF45","doi-asserted-by":"crossref","unstructured":"Unhavaithaya, Y., Shin, T. H., Miliaras, N., Lee, J., Oyama, T. and Mello, C. C. (2002). MEP-1 and a homolog of the NURD complex component Mi-2 act together to maintain germline-soma distinctions in C. elegans. Cell111,991-1002.","DOI":"10.1016\/S0092-8674(02)01202-3"},{"key":"2021042605320351200_REF46","doi-asserted-by":"crossref","unstructured":"Vojtek, A. B., Hollenberg, S. M. and Cooper, J. A.(1993). Mammalian Ras interacts directly with the serine\/threonine kinase Raf. Cell74,205-214.","DOI":"10.1016\/0092-8674(93)90307-C"},{"key":"2021042605320351200_REF47","doi-asserted-by":"crossref","unstructured":"Wade, P. A., Jones, P. L., Vermaak, D. and Wolffe, A. P.(1998). A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Curr. Biol.8,843-846.","DOI":"10.1016\/S0960-9822(98)70328-8"},{"key":"2021042605320351200_REF48","doi-asserted-by":"crossref","unstructured":"Wu, Y. and Han, M. (1994). Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegansSur-1 MAP kinase in vulval differentiation. Genes Dev.8, 147-159.","DOI":"10.1101\/gad.8.2.147"},{"key":"2021042605320351200_REF49","doi-asserted-by":"crossref","unstructured":"Xue, Y., Wong, J., Moreno, G. T., Young, M. K., Cote, J. and Wang, W. (1998). NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol. Cell2,851-861.","DOI":"10.1016\/S1097-2765(00)80299-3"},{"key":"2021042605320351200_REF50","doi-asserted-by":"crossref","unstructured":"Yang, S. H., Jaffray, E., Hay, R. T. and Sharrocks, A. D.(2003). Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity. Mol. Cell12, 63-74.","DOI":"10.1016\/S1097-2765(03)00265-X"},{"key":"2021042605320351200_REF51","doi-asserted-by":"crossref","unstructured":"Yang, S. H. and Sharrocks, A. D. (2004). SUMO promotes HDAC-mediated transcriptional repression. Mol. Cell13,611-617.","DOI":"10.1016\/S1097-2765(04)00060-7"},{"key":"2021042605320351200_REF52","doi-asserted-by":"crossref","unstructured":"Zhang, Y., LeRoy, G., Seelig, H. P., Lane, W. S. and Reinberg,D. (1998). The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell95,279-289.","DOI":"10.1016\/S0092-8674(00)81758-4"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/132\/5\/1047\/1553917\/1047.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/132\/5\/1047\/1553917\/1047.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T15:54:35Z","timestamp":1625414075000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/132\/5\/1047\/43254\/Sumoylation-of-LIN-1-promotes-transcriptional"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,1]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2005,3,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.01664","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2005,3,1]]}}}