Human HTm4 is a hematopoietic cell cycle regulator
Human HTm4 is a hematopoietic cell cycle regulator
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DOI：
10.1172/jci14025
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发表时间：
2002-01-01
影响因子：
15.9
通讯作者：
Adra, CN
中科院分区：
文献类型：
--
作者：
Donato, JL;Ko, J;Adra, CN
适当控制细胞周期进程对于造血系统的持续自我更新、分化和稳态至关重要。所有类型的细胞都有共同的细胞周期调节因子。从广义上讲，共同调节因子的不同表达模式定义了细胞类型或谱系特异性。然而，仍然有可能根据造血系统的需要定制造血细胞周期调节因子。在这里，我们描述了一种新的蛋白质，HTm4，它作为造血细胞周期调节因子。我们的数据表明，HTm4在造血组织中表达，并在造血干细胞分化过程中受到严格调控。它与细胞周期蛋白依赖性激酶相关（cdk相关）磷酸酶cdk2 （KAP-CDK2）复合物结合，这三种蛋白在人淋巴组织中表现出相似的细胞表达模式。HTm4刺激KAP的磷酸酶活性，其c端区域是KAP- cdk2复合物结合和KAP活性调节所必需的。HTm4过表达可导致细胞周期阻滞在G(0)/G(1)期。因此，HTm4是G(1)-S细胞周期转变的一种新型造血调节剂。
Proper control of cell cycle progression is critical for the constant self-renewal, differentiation, and homeostasis of the hematopoietic system. Cells of all types share the common cell cycle regulators. The different expression patterns of common regulators, in a broad sense, define cell-type or lineage specificity. However, there remains the possibility of hematopoietic cell cycle regulators tailored to the demands of the hematopoietic system. Here we describe a novel protein, HTm4, which serves as a hematopoietic cell cycle regulator. Our data indicate that HTm4 is expressed in hematopoietic tissues and is tightly regulated during the differentiation of hematopoietic stem cells. It binds to cyclin-dependent kinase-associated (CDK-associated) phosphatase-CDK2 (KAP-CDK2) complexes, and the three proteins demonstrate similar patterns of cellular expression in human lymphoid tissues. HTm4 stimulates the phosphatase activity of KAP, and its C-terminal region is required for binding to KAP-CDK2 complexes and the modulation of KAP activity. Overexpression of HTm4 can cause cell cycle arrest at the G(0)/G(1) phase. Thus, HTm4 is a novel hematopoietic modulator for the G(1)-S cell cycle transition.