Inhibition of c-myc expression induces apoptosis of WEHI 231 murine B cells.
Inhibition of c-myc expression induces apoptosis of WEHI 231 murine B cells.
复制标题
抑制 c-myc 表达可诱导 WEHI 231 小鼠 B 细胞凋亡。
DOI：
10.1128/mcb.16.9.5015
复制
发表时间：
1996
影响因子：
5.3
通讯作者：
Sonenshein,GE
中科院分区：
文献类型：
--
作者：
Wu,M;Arsura,M;Bellas,RE;FitzGerald,MJ;Lee,H;Schauer,SL;Sherr,DH;Sonenshein,GE
WEHI 231未成熟B淋巴瘤细胞用针对其表面免疫球蛋白的抗体（抗Ig）处理诱导细胞凋亡，并且已经作为B细胞耐受的模型被广泛研究。抗-Ig治疗指数生长的WEHI 231细胞导致c-myc表达的早期瞬时增加，随后下降至低于基础水平; c-myc表达的这种下降紧接在诱导细胞死亡之前。在此，我们调节了NF-κB/Rel因子的活性，该因子调节c-myc基因转录的速率，以确定c-Myc水平的增加或减少是否介导WEHI 231细胞的凋亡。加入丝氨酸/苏氨酸蛋白酶抑制剂或N-甲苯磺酰基-L-苯丙氨酸氯甲基酮（TPCK），可阻断这些细胞中NF-κB/Rel IκBα特异性抑制剂的正常快速周转，导致Rel相关因子结合下降。TPCK治疗导致c-myc表达降低，阻止了抗Ig治疗后常见的增加。而抑制c-myc的表达诱导的抗-Ig未能阻断凋亡，c-myc的表达减少在指数增长WEHI 231细胞诱导凋亡，即使在没有抗-Ig治疗。在异位表达c-Myc的WEHI 231克隆中，由TPCK或抗Ig处理诱导的凋亡显著减少，细胞继续增殖。此外，WEHI 231细胞的凋亡后，Mad 1的表达增强，这已被发现降低功能性c-Myc水平。这些结果表明，NF-κ B/Rel结合的下降导致的c-myc表达的下降导致WEHI 231 B细胞凋亡的激活。
Treatment of WEHI 231 immature B-lymphoma cells with an antibody against their surface immunoglobulin (anti-Ig) induces apoptosis and has been studied extensively as a model of B-cell tolerance. Anti-Ig treatment of exponentially growing WEHI 231 cells results in an early transient increase in c-mycexpression that is followed by a decline to below basal levels; this decrease in c-myc expression immediately precedes the induction of cell death. Here we have modulated NF-κB/Rel factor activity, which regulates the rate of c-myc gene transcription, to determine whether the increase or decrease in c-Myc levels mediates apoptosis in WEHI 231 cells. Addition of the serine/threonine protease inhibitorN-tosyl-l-phenylalanine chloromethyl ketone (TPCK), which blocks the normally rapid turnover of the specific inhibitor of NF-κB/Rel IκBα in these cells, caused a drop in Rel-related factor binding. TPCK treatment resulted in decreased c-mycexpression, preventing the usual increase seen following anti-Ig treatment. Whereas inhibition of the induction of c-myc expression mediated by anti-Ig failed to block apoptosis, reduction of c-mycexpression in exponentially growing WEHI 231 cells induced apoptosis even in the absence of anti-Ig treatment. In WEHI 231 clones ectopically expressing c-Myc, apoptosis induced by treatment with TPCK or anti-Ig was significantly diminished and cells continued to proliferate. Furthermore, apoptosis of WEHI 231 cells ensued following enhanced expression of Mad1, which has been found to reduce functional c-Myc levels. These results indicate that the decline in c-mycexpression resulting from the drop in NF-kB/Rel binding leads to activation of apoptosis of WEHI 231 B cells.