The Shwachman-Diamond SBDS protein localizes to the nucleolus
The Shwachman-Diamond SBDS protein localizes to the nucleolus
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DOI：
10.1182/blood-2005-02-0807
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发表时间：
2005-08-15
期刊：
影响因子：
20.3
通讯作者：
Shimamura, A
中科院分区：
文献类型：
--
作者：
Austin, KM;Leary, RJ;Shimamura, A
Shwachman-Diamond综合征（SDS）是一种以胰腺外分泌功能不全和骨髓衰竭为特征的常染色体隐性遗传性疾病。我们的特点是Shwachman-Bodian-Diamond综合征（SBDS）蛋白表达和细胞内定位在7例SDS患者和健康对照。如基因突变所预测的，4例SDS患者未表现出可检测到的全长SBDS蛋白。对于IVS 2 + 2 T>C剪接供体突变为纯合子的患者DF 277表达了少量水平的SBDS蛋白。患者SD 101表达低水平的SBDS蛋白，其携带R169 C错义突变。未携带可检测基因突变的患者DF 269表达野生型水平的SBDS蛋白，以进一步支持可能导致疾病表型发病机制的其他基因的证据。SBDS蛋白在正常对照成纤维细胞的细胞核和细胞质中检测到，但特别集中在核仁内。SBDS定位是细胞周期依赖性的，在G（1）和G（2）期间核仁定位，在S期期间弥散核定位。SD 101和DF 269中SBDS核仁定位是完整的。SBDS的核仁内定位为其在rRNA加工中的假定作用提供了进一步的支持性证据。
Shwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder characterized by exocrine pancreatic insufficiency and bone marrow failure, The gene for this syndrome, SBDS, encodes a highly conserved novel protein. We characterized Shwachman-Bodian-Diamond syndrome (SBDS) protein expression and intracellular localization in 7 patients with SDS and healthy controls. As predicted by gene mutation, 4 patients with SDS exhibited no detectable full-length SBDS protein. Patient DF277, who was homozygous for the IVS2 + 2 T>C splice donor mutation, expressed scant levels of SBDS protein. Patient SD101 expressed low levels of SBDS protein harboring an R169C missense mutation. Patient DF269, who carried no detectable gene mutations, expressed wild-type levels of SBDS protein to add further support to the growing body of evidence for additional gene(s) that might contribute to the pathogenesis of the disease phenotype. The SBDS protein was detected in both the nucleus and the cytoplasm of normal control fibroblasts, but was particularly concentrated within the nucleolus. SBDS localization was cell-cycle dependent, with nucleolar localization during G(1) and G(2) and diffuse nuclear localization during S phase. SBDS nucleolar localization was intact in SD101 and DF269. The intranucleolar localization of SBDS provides further Supportive evidence for its Postulated role in rRNA processing.