Mcl-1, a Bcl-2 family member, delays the death of hematopoietic cells under a variety of apoptosis-inducing conditions
Mcl-1, a Bcl-2 family member, delays the death of hematopoietic cells under a variety of apoptosis-inducing conditions
复制标题
DOI：
10.1182/blood.v89.2.630
复制
发表时间：
1997-01-15
期刊：
影响因子：
20.3
通讯作者：
Craig, RW
中科院分区：
文献类型：
--
作者：
Zhou, P;Qian, LP;Craig, RW
Mcl-1是Bcl-2家族的成员，其基于在经历分化的成髓细胞白血病细胞中表达增加而被鉴定。Mcl-1以前被发现在中国仓鼠卵巢细胞中引起凋亡细胞死亡延迟方面与Bcl-2相似。这里描述的工作旨在确定Mcl-1是否也可以在造血细胞中发挥这种作用，因为内源性Mcl-1表达在造血系统中是突出的。另一个目的是评估Mcl-1在暴露于各种细胞毒性刺激的细胞中的作用，因为已知Bcl-2具有广谱活性。为了达到这些目的，FDC-P1鼠骨髓祖细胞转染载体驱动组成型或诱导型表达的Mcl-1。发现引入的Mcl-1基因在引起凋亡性细胞死亡的各种条件下引起存活力的延长，所述条件包括暴露于细胞毒性剂（化疗药物依托泊苷、钙离子载体或UV照射）和撤回所需的生长因子。此外，发现Mcl-1与Bar相互作用，Bar是Bcl-2家族的成员，其作为同源二聚体促进细胞死亡，但可以与Bcl-2异源二聚体化以促进细胞活力。尽管Mcl-1延长了细胞活力，但在连续暴露于细胞毒性剂时，它并不能阻止最终的细胞死亡。延长的生存能力是最大的Mcl-1的表达诱导之前的应用程序的凋亡刺激，虽然发生一些增加，如果Mcl-1诱导后不久，在明显的凋亡。总的来说，这些发现提供了Mcl-1和Bcl-2之间的进一步相似之处，表明Mcl-1可以与造血FDC-P1细胞中的Bar相互作用，并可以在多种细胞毒性条件下延长细胞活力。(C)1997年，美国血液学会。
Mcl-1 is a member of the Bcl-2 family that was identified based on increased expression in myeloblastic leukemia cells undergoing differentiation. Mcl-1 was previously found to be similar to Bcl-2 in causing a delay in apoptotic cell death in Chinese hamster ovary cells. The work described here was aimed at determining whether Mcl-1 could also exert such an effect in hematopoietic cells, because endogenous Mcl-1 expression is prominent in the hematopoietic system. A further aim was to assess the effects of Mcl-1 in cells exposed to a variety of cytotoxic stimuli, because Bcl-2 is known to have a broad spectrum of activity. To approach these aims, FDC-P1 murine myeloid progenitor cells were transfected with vectors driving either constitutive or inducible expression of Mcl-1. The introduced Mcl-1 gene was found to cause a prolongation of viability under Various conditions that cause apoptotic cell death, including exposure to cytotoxic agents (the chemotherapeutic drug etoposide, calcium ionophore, or UV irradiation) and the withdrawal of required growth factors. In addition, Mcl-1 was found to interact with Bar, a member of the Bcl-2 family that promotes cell death as a homodimer but that can heterodimerize with Bcl-2 to promote cell viability. Although Mcl-1 prolonged cell viability, it did not prevent eventual cell death upon continuous exposure to a cytotoxic agent. Prolongation of viability was maximal when expression of Mcl-1 was induced before the application of the apoptotic stimulus, although some increase occurred if Mcl-1 was induced shortly thereafter and before overt apoptosis. Taken as a whole, these findings provide further parallels between Mcl-1 and Bcl-2, showing that Mcl-1 can interact with Bar in hematopoietic FDC-P1 cells and can prolong cell viability under a variety of cytotoxic conditions. (C) 1997 by The American Society of Hematology.