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Here we reports a mechanism of BCR ligation\u2010induced apoptosis involving protein phosphatase calcineurin and its specific substrate, transcriptional factor NF\u2010AT. In response to BCR cross\u2010linking, endogenous calcineurin was rapidly activated, and this facilitated nuclear translocation of NF\u2010ATc2, a subtype of NF\u2010AT members. Interestingly, nuclear\u2010imported NF\u2010ATc2 functioned pro\u2010apoptotically in BL cells. The effect of NF\u2010ATc2 was efficiently blocked with FK506, which prevented its nuclear translocation through inactivation of calcineurin. In addtion, TR3 induction during BCR cross\u2010linking was reduced by FK506 and the VIVIT peptide, which is a highly selective inhibitor for NF\u2010AT. This strongly suggests that activation of NF\u2010ATc2 by calcineurin is essential for TR3 recruitment, and that TR3 can be considered as a candidate for death effector in BCR\u2010mediated apoptosis. Therefore, NF\u2010ATc2 plays a crucial role in BCR\u2010mediated apoptosis in type IBL, providing greater insight into unique BL characteristics through BCR signaling.<\/jats:p>","DOI":"10.1002\/immu.200390000","type":"journal-article","created":{"date-parts":[[2003,2,19]],"date-time":"2003-02-19T19:15:48Z","timestamp":1045682148000},"page":"1-11","source":"Crossref","is-referenced-by-count":31,"title":["NF\u2010ATc2 induces apoptosis in Burkitt's lymphoma cells through signaling via the B cell antigen receptor"],"prefix":"10.1002","volume":"33","author":[{"given":"Eisaku","family":"Kondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Harashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takami","family":"Takabatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunzo","family":"Orita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadaatsu","family":"Akagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,12,13]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.5.1361.1361"},{"key":"e_1_2_7_2_2","unstructured":"Jaffe E. S. Harris N. L.andStein H. N. Tumors of haematopoietic and lymphoid tissues. World Health Organization classification of tumors.IARCP Press Lyon2001 pp181\u2013184."},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.555"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.139.1.313"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","first-page":"4404","DOI":"10.4049\/jimmunol.154.9.4404","article-title":"Engagement of the antigen\u2010receptor on immature murineB lymphocytes results in death by apoptosis.","volume":"154","author":"Norvell A.","year":"1995","journal-title":"J. Immunol."},{"key":"e_1_2_7_6_2","first-page":"4404","article-title":"Mechanism of antigen receptor\u2010dependent apoptosis of human B lymphoma cells probed with a panel of 27 monoclonal antibodies.","volume":"154","author":"Grafton G.","year":"1997","journal-title":"Cell. 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