Non-Diamond Blackfan Anemia Disorders of Ribosome Function: Shwachman Diamond Syndrome and 5q-Syndrome
Non-Diamond Blackfan Anemia Disorders of Ribosome Function: Shwachman Diamond Syndrome and 5q-Syndrome
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DOI：
10.1053/j.seminhematol.2011.01.002
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发表时间：
2011-04-01
影响因子：
3.6
通讯作者：
Liu, Johnson M.
中科院分区：
文献类型：
--
作者：
Burwick, Nicholas;Shimamura, Akiko;Liu, Johnson M.
许多被称为核糖体病的人类疾病与受损的核糖体生物发生或功能有关。这些包括但不限于钻石-布莱克凡贫血（DBA）、Shwachman Diamond综合征（SDS）和5 q-骨髓增生异常综合征（MDS）。本文综述了后两种非DBA的核糖体功能障碍。SDS和5 q综合征都导致造血功能受损和白血病易感性。由于SBDS基因的双等位基因突变，SDS是一种多系统疾病，还包括骨骼异常、胰腺和神经认知功能障碍。SBDS与人细胞中的60 S亚基相关，并在酵母模型中的亚基连接和翻译激活中发挥作用。相比之下，5 q综合征与获得性RPS 14单倍不足相关，RPS 14是小40 S亚基的组成部分。RPS 14对于酵母模型中的40 S组装是关键的，并且人CD 34（+）细胞中RPS 14的消耗足以重现5 q-红细胞缺陷。SDS和5 q综合征都代表了核糖体功能的重要模型，并可能为核糖体病的未来治疗策略提供信息。Semin Hematol 48：136-143. (C)2011 Elsevier Inc. All rights reserved.
A number of human disorders, dubbed ribosomopathies, are linked to impaired ribosome biogenesis or function. These include but are not limited to Diamond Blackfan anemia (DBA), Shwachman Diamond syndrome (SDS), and the 5q- myelodysplastic syndrome (MDS). This review focuses on the latter two non-DBA disorders of ribosome function. Both SDS and 5q- syndrome lead to impaired hematopoiesis and a predisposition to leukemia. SDS, due to bi-allelic mutations of the SBDS gene, is a multi-system disorder that also includes bony abnormalities, and pancreatic and neurocognitive dysfunction. SBDS associates with the 60S subunit in human cells and has a role in subunit joining and translational activation in yeast models. In contrast, 5q- syndrome is associated with acquired haplo-insufficiency of RPS14, a component of the small 40S subunit. RPS14 is critical for 40S assembly in yeast models, and depletion of RPS14 in human CD34(+) cells is sufficient to recapitulate the 5q- erythroid defect. Both SDS and the 5q- syndrome represent important models of ribosome function and may inform future treatment strategies for the ribosomopathies. Semin Hematol 48:136-143. (C) 2011 Elsevier Inc. All rights reserved.