MCL1, A GENE EXPRESSED IN PROGRAMMED MYELOID CELL-DIFFERENTIATION, HAS SEQUENCE SIMILARITY TO BCL2
MCL1, A GENE EXPRESSED IN PROGRAMMED MYELOID CELL-DIFFERENTIATION, HAS SEQUENCE SIMILARITY TO BCL2
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DOI：
10.1073/pnas.90.8.3516
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
CRAIG, RW
中科院分区：
文献类型：
--
作者：
KOZOPAS, KM;YANG, T;CRAIG, RW
在它们的生命周期中，未成熟的细胞通常会经历一系列的转变，进入分化状态，最终经历细胞死亡。这种进展在癌症中是异常的，尽管向分化的过渡可以在可诱导的白血病细胞细小中重建。本报告描述了我们在佛波酯诱导单核/巨噬细胞分化过程中从ML-1人髓系白血病细胞系中分离到的一个基因MCL1。我们的结果表明，MCL1的表达在ML-1诱导分化的早期(1-3小时)，在分化标记和成熟形态出现之前(1-3天)增加。他们进一步表明，MCL1与BCL2具有序列相似性，BCL2参与了正常淋巴发育和t(14；18)染色体易位的淋巴瘤。MCL1和BCL2不属于已知的基因家族。BCL2与许多癌基因的不同之处在于，它抑制细胞程序性死亡，促进活性而不是增殖；这与MCL1与分化的编程以及伴随而来的维持活性而不是增殖的关联是平行的。因此，与增殖相关基因不同，MCL1和BCL2的表达与细胞分化和细胞存活/死亡的编程有关。MCL1的发现拓宽了我们对新出现的MCL1/BCL2基因家族的认识，并将使我们能够进一步与癌基因家族进行比较。
During their lifespan, immature cells normally pass through sequential transitions to a differentiated state and eventually undergo cell death. This progression is aberrant in cancer, although the transition to differentiation can be reestablished in inducible leukemia cell fines. This report describes a gene, MCL1, that we isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway. Our results demonstrate that expression of MCL1 increases early in the induction, or ''programming,'' of differentiation in ML-1 (at 1-3 hr), before the appearance of differentiation markers and mature morphology (at 1-3 days). They further show that MCL1 has sequence similarity to BCL2, a gene involved in normal lymphoid development and in lymphomas with the t(14;18) chromosome translocation. MCL1 and BCL2 do not fall into previously known gene families. BCL2 differs from many oncogenes in that it inhibits programmed cell death, promoting viability rather than proliferation; this parallels the association of MCL1 with the programming of differentiation and concomitant maintenance of viability but not proliferation. Thus, in contrast to proliferation-associated genes, expression of MCL1 and BCL2 relates to the programming of differentiation and cell viability/death. The discovery of MCL1 broadens our perspective on an emerging MCL1/BCL2 gene family and will allow further comparison with oncogene families.