{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T11:32:29Z","timestamp":1792755149050,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,8,26]],"date-time":"2009-08-26T00:00:00Z","timestamp":1251244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Understanding the underlying mechanisms by which a normal cell avoids the oncogenic potential of MUC1 signaling requires further definition of the pathways by which the MUC1 cytoplasmic tail is processed in both normal and tumor\u2010derived cells. In the present study we describe the processing pathway initiated by TACE\/ADAM17 cleavage of MUC1. Utilizing the human uterine epithelial cell line, HES, derived from normal endometrium, we show that endogenous full length MUC1 undergoes regulated intramembranous proteolysis mediated by presenillin\u2010dependent \u03b3\u2010secretase. Cytokine\u2010stimulated HES cells exposed to \u03b3\u2010secretase inhibitors accumulated a membrane\u2010associated 15\u2009kDa fragment of the MUC1 C\u2010terminal subunit (CTF15). Inhibitors of TACE\/ADAM17\u2010mediated shedding inhibited accumulation of MUC1\u2010CTF15 and MUC1 ectodomain release to a similar extent consistent with MUC1\u2010CTF15 being a product of TACE\/ADAM17 action. Reduction of catalytically active \u03b3\u2010secretase complex by nicastrin siRNA treatment also resulted in CTF15 accumulation. Furthermore, mature nicastrin, the substrate receptor for \u03b3\u2010secretase, co\u2010immunoprecipitated with CTF15 in the presence of \u03b3\u2010secretase inhibitors indicating the formation of CTF15: nicastrin complexes. MUC1\u2010CTF15 accumulation in response to \u03b3\u2010secretase inhibition was demonstrated in both normal and tumor\u2010derived cells from humans and mice indicating that this processing pathway exists in many cell contexts. We did not detect products of MUC1 cleavage by \u03b3\u2010secretase in the presence of various proteasomal inhibitors indicating that subsequent degradation is either non\u2010proteasomal or extremely efficient. We suggest that this efficient pathway attenuates potential signaling mediated by cytoplasmic tail fragments. J. Cell. Biochem. 108: 802\u2013815, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22292","type":"journal-article","created":{"date-parts":[[2009,8,26]],"date-time":"2009-08-26T23:44:12Z","timestamp":1251330252000},"page":"802-815","source":"Crossref","is-referenced-by-count":48,"title":["MUC1 is a substrate for \u03b3\u2010secretase"],"prefix":"10.1002","volume":"108","author":[{"given":"JoAnne","family":"Julian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraja","family":"Dharmaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Carson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,8,26]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1552","article-title":"The breast cancer\u2010associated MUC1 gene generates both a receptor and its cognate binding protein","volume":"59","author":"Baruch A","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409272200"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200104045"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(02)00104-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01381-0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.132277899"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20030282"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011379725811"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.03.080"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100357200"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/10.5.439"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-1-44"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00352-2"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204446200"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1406"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00901.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703222200"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506047200"},{"key":"e_1_2_6_20_1","first-page":"765","article-title":"Heregulin targets gamma\u2010catenin to the nucleolus by a mechanism dependent on the DF3\/MUC1 oncoprotein","volume":"1","author":"Li Y","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42677-4"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01260-9"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00385.2003"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.09.065"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1035"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002054"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050491"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(03)00041-X"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301360200"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065412"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwj110"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.45.28128"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209976"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.07.031"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm954"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(04)00020-0"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209012"},{"issue":"1","key":"e_1_2_6_38_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1042\/bj3470131","article-title":"Intracellular maturation and localization of the tumour necrosis factor alpha convertase (TACE)","volume":"347","author":"Schlondorff J","year":"2000","journal-title":"Biochem J"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011248200"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.022"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300095200"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4647"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01159-1"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00061-7"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040513"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208326200"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0399"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-06-0038"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M400333-JLR200"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.4.995"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/172460080001500413"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.107.064584"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.22292","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.22292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T08:30:40Z","timestamp":1752913840000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.22292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,26]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,11]]}},"alternative-id":["10.1002\/jcb.22292"],"URL":"https:\/\/doi.org\/10.1002\/jcb.22292","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,26]]}}}