Anamorsin, anti-apoptotic molecule, and hematopoiesis

许多生长因子和细胞因子阻止细胞凋亡。利用表达克隆方法，我们鉴定了一个新的抗凋亡分子Anamorsin，它与Bcl-2家族、caspase家族或信号转导分子等Down细胞凋亡调节分子没有同源性。Anamorsin的表达完全依赖于生长因子的刺激，如白细胞介素3、干细胞因子和血小板生成素在因子依赖性的造血细胞系中，Anamorsin的强制表达赋予了对生长因子剥夺引起的细胞凋亡的体外抗性。此外，Anamorsin在体内被发现作为一种抗凋亡分子，因为Anamorsin -/-小鼠在妊娠后期因胎儿肝脏最终造血功能缺陷而死亡（FL）。虽然这些小鼠FL中的造血干细胞/祖细胞的数量没有减少，但响应细胞因子的髓系，特别是红系集落形成受到严重破坏。此外，Anamorsin -/-红细胞在终末成熟过程中启动凋亡。对于Anamorsin介导的细胞存活机制，微阵列分析显示，Anamorsin- /-小鼠FL中Bcl-xL和Jak2的表达严重受损。因此，Anamorsin被认为是造血的必要分子，介导各种细胞因子的抗凋亡作用。

Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to Down apoptosis regulatory molecules such as Bcl-2 family, caspase family, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors, such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin -/- mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin -/- erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin -/- mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokies.