{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:19:22Z","timestamp":1792174762352,"version":"4.4.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>TGF-\u03b2 is a potent inducer of apoptosis in many Burkitt\u2019s lymphoma (BL) cell lines. In this study, we characterize this apoptotic process in the EBV-negative BL41 cell line. Induction of apoptosis was detected as early as 8 h after TGF-\u03b2 treatment, as assayed by TUNEL and poly(ADP-ribose) polymerase cleavage. FACS analysis demonstrates that this proceeds predominately from the G1, but also from the G2\/M phases of the cell cycle. We observed no early detectable changes in the steady-state levels of Bcl-2 and several of its family members after TGF-\u03b2 treatment. We detected cleavage of caspases 2, 3, 7, 8, and 9 into their active subunits. Consistent with the involvement of these enzymes in TGF-\u03b2-mediated apoptosis, the broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(Ome)-flouromethylketone (ZVAD-fmk) blocked TGF-\u03b2-induced apoptosis and revealed a G1 arrest in treated cells. Use of specific caspase inhibitors revealed that the induction of apoptosis is caspase 8 dependent, but caspase 3 independent. Activation of caspase 8 has been shown to be a critical event in death receptor-mediated apoptosis. However, TGF-\u03b2 treatment of BL41 cells was found not to affect the cell surface expression of Fas, TNF-R1, DR3, DR4, or DR5, or the steady-state expression levels of Fas ligand, TNF-R1, DR3, DR4, and DR5. Furthermore, blocking experiments indicated that TGF-\u03b2-mediated apoptosis is not dependent on Fas ligand, TNF-\u03b1, tumor necrosis-like apoptosis-inducing ligand, or TNF-like weak inducer of apoptosis signaling. Therefore, it appears that TGF-\u03b2 induces apoptosis in BL cell lines via caspase 8 in a death receptor-independent fashion.<\/jats:p>","DOI":"10.4049\/jimmunol.165.5.2500","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T17:58:09Z","timestamp":1398189489000},"page":"2500-2510","source":"Crossref","is-referenced-by-count":70,"title":["Apoptosis Induced by TGF-\u03b21 in Burkitt\u2019s Lymphoma Cells Is Caspase 8 Dependent But Is Death Receptor Independent"],"prefix":"10.1093","volume":"165","author":[{"given":"Gareth J","family":"Inman","sequence":"first","affiliation":[{"name":"Section of Virology and Cell Biology and the Ludwig Institute for Cancer Research, Imperial College of Science, Technology and Medicine , St. Mary\u2019s Campus, London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J","family":"Allday","sequence":"additional","affiliation":[{"name":"Section of Virology and Cell Biology and the Ludwig Institute for Cancer Research, Imperial College of Science, Technology and Medicine , St. Mary\u2019s Campus, London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,9,1]]},"reference":[{"key":"2026020213075209500_R1","first-page":"383","volume-title":"Annu. 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