Regulation of hematopoietic stem cell fate by the ubiquitin proteasome system.
Regulation of hematopoietic stem cell fate by the ubiquitin proteasome system.
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DOI：
10.1016/j.it.2012.01.009
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发表时间：
2012-07
影响因子：
16.8
通讯作者：
Aifantis I
中科院分区：
文献类型：
--
作者：
Moran-Crusio K;Reavie LB;Aifantis I
造血干细胞（HSCs）是造血干细胞的一种。这是通过仔细调节HSC活性以平衡静止、自我更新和分化来实现的。对HSC维持的分子机制的研究主要集中在信号传导和转录过程的作用。然而，最近已经证明，通过泛素蛋白酶体系统（UPS）的蛋白质调节是至关重要的正常HSC功能。一旦失去就可能导致转化和白血病。在治疗套细胞淋巴瘤和多发性骨髓瘤中有效使用UPS的一般和可逆抑制剂Bortezavine证明了靶向UPS具有治疗潜力。因此，了解UPS如何调节HSC活性的新兴领域可能会导致白血病治疗的新靶点。
Hematopoietic stem cells (HSCs) residing in the bone marrow generate mature blood cells throughout the life of the organism. This is accomplished by careful regulation of HSC activity to balance quiescence, self-renewal and differentiation. Studies of the molecular mechanisms governing HSC maintenance have mostly focused on the role of signaling and transcriptional processes. However, it has recently been demonstrated that protein regulation via the ubiquitin proteasome system (UPS) is crucial for normal HSC function. The loss of which can lead to transformation and leukemogenesis. The effective use of a general and reversible inhibitor of the UPS, Bortezomib, in treating mantle cell lymphoma and multiple myeloma demonstrated that targeting the UPS has therapeutic potential. Thus, understanding the emerging field of how the UPS regulates HSC activity may lead to novel targets for therapy of leukemia.
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