ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells
ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells
复制标题
DOI：
10.1074/jbc.274.48.33835
复制
发表时间：
1999-11-26
影响因子：
4.8
通讯作者：
Sagara, J
中科院分区：
文献类型：
--
作者：
Masumoto, J;Taniguchi, S;Sagara, J
使用单克隆抗体 (mAb) 鉴定了与细胞凋亡相关的形态变化的细胞骨架和/或核基质分子。我们开发了针对用全反式视黄酸预处理的 HL-60 细胞的 Triton X-100 不溶成分的单克隆抗体。特别是，一种 mAb 识别了一种 22 kDa 的蛋白质，该蛋白质在视黄酸和其他抗肿瘤药物诱导的细胞凋亡过程中形成聚集体并表现为斑点，从而表现出有趣的行为。其 cDNA 的克隆和测序表明，该蛋白质包含 195 个氨基酸，其 C 末端一半具有半胱天冬酶募集结构域 (CARD) 基序，这是参与细胞凋亡信号传导的众多蛋白质的特征。我们将该蛋白称为 ASC（含有 CARD 的凋亡相关斑点样蛋白）。 ASC 基因定位于染色体 16p11.2-12。研究发现ASC的反义寡核苷酸可降低ASC的表达，从而抑制依托泊苷介导的HL-60细胞凋亡。我们的结果表明 ASC 是包含 CARD 的接头蛋白家族的新成员。
The cytoskeletal and/or nuclear matrix molecules responsible for morphological changes associated with apoptosis were identified using monoclonal antibodies (mAbs). We developed mAbs against Triton X-100-insoluble components of HL-60 cells pretreated with all-trans retinoic acid. In particular, one mAb recognized a 22-kDa protein that exhibited intriguing behavior by forming an aggregate and appearing as a speck during apoptosis induced by retinoic acid and other anti-tumor drugs. Cloning and sequencing of its cDNA revealed that this protein comprises 195 amino acids and that its C-terminal half has a caspase recruitment domain (CARD) motif, characteristic of numerous proteins involved in apoptotic signaling. We referred to this protein as ASC (apoptosis-associated Speck-like protein containing a CARD). The ASC gene was mapped on chromosome 16p11.2-12. The antisense oligonucleotides of ASC were found to reduce the expression of ASC, and consequently, etoposide-mediated apoptosis of HL-60 cells was suppressed. Our results indicate that ASC is a novel member of the CARD-containing adaptor protein family.