Inflammation-associated cell cycle-independent block of apoptosis by survivin in terminally differentiated neutrophils.
Inflammation-associated cell cycle-independent block of apoptosis by survivin in terminally differentiated neutrophils.
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在终末分化的中性粒细胞中，源源凋亡与炎症相关的细胞周期无关。
DOI：
10.1084/jem.20032033
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发表时间：
2004-05-17
影响因子：
15.3
通讯作者：
Simon, HU
中科院分区：
文献类型：
--
作者：
Altznauer, F;Martinelli, S;Yousefi, S;Thürig, C;Schmid, I;Conway, EM;Schöni, MH;Vogt, P;Mueller, C;Fey, MF;Zangemeister-Wittke, U;Simon, HU
由于Survivin在多种肿瘤中的表达及其作为肿瘤治疗靶点的潜力，其研究受到了广泛关注。生存素的表达被描述为细胞周期依赖性的，并且仅限于G2-M检查点，在那里它抑制增殖细胞中的凋亡。与目前的观点一致，我们发现存活素在分化过程中增殖的未成熟中性粒细胞中高表达。与未成熟的细胞相比，成熟的中性粒细胞只含有很少或没有生存素蛋白。引人注目的是，这些细胞在体外和体内炎症条件下，在粒细胞/巨噬细胞集落刺激因子（CSF）或粒细胞CSF刺激后重新表达生存素。此外，生存素缺陷的成熟中性粒细胞在生存因子暴露后不能增加其寿命。总之，我们的研究结果表明：（a）生存素的过度表达发生在原代，甚至终末分化的细胞，并不限于增殖细胞;和（B）生存素作为一种抑制剂的凋亡蛋白在细胞周期无关的方式。因此，生存素在维持G2-M检查点和凋亡控制中起着独特和独立的作用，并且其过表达不限于增殖细胞。这些数据提供了新的见解生存素的调节和功能，并具有重要的意义，炎症性疾病和癌症的发病机制，诊断和治疗。
Survivin has received great attention due to its expression in many human tumors and its potential as a therapeutic target in cancer. Survivin expression has been described to be cell cycle–dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells. In agreement with this current view, we found that survivin expression was high in immature neutrophils, which proliferate during differentiation. In contrast with immature cells, mature neutrophils contained only little or no survivin protein. Strikingly, these cells reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF) or granulocyte CSF stimulation in vitro and under inflammatory conditions in vivo. Moreover, survivin-deficient mature neutrophils were unable to increase their lifespan after survival factor exposure. Together, our findings demonstrate the following: (a) overexpression of survivin occurs in primary, even terminally differentiated cells and is not restricted to proliferating cells; and (b) survivin acts as an inhibitor of apoptosis protein in a cell cycle–independent manner. Therefore, survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells. These data provide new insights into the regulation and function of survivin and have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases and cancer.
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影响因子：
4.8
作者：
Altznauer, F;Conus, S;Simon, HU
通讯作者：
Simon, HU
影响因子：
2.8
作者：
Daigle, I;Simon, HU
通讯作者：
Simon, HU
影响因子：
2.2
作者：
Cowland, JB;Borregaard, N
通讯作者：
Borregaard, N
影响因子：
20.3
作者：
Fukuda, S;Pelus, LM
通讯作者：
Pelus, LM
影响因子：
7.2
作者：
Holcik, M;Gibson, H;Korneluk, RG
通讯作者：
Korneluk, RG