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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18860

Title: Mechanisms of Erythropoietic Failure in Shwachman Diamond Syndrome Caused by Loss of the Ribosome-related Protein, SBDS
Authors: Sen, Saswati
Advisor: Dror, Yigal
Department: Medical Science
Keywords: Erythropoiesis
Shwachman Diamond Syndrome
Issue Date: 15-Feb-2010
Abstract: Anemia occurs in 60% of patients with Shwachman Diamond Syndrome (SDS). Although bi-allelic mutations in SBDS cause SDS, it is unclear whether SBDS is critical for erythropoiesis and what the pathogenesis of anemia is in SDS. I hypothesize that SBDS protects early erythroid progenitors from p53 family member mediated apoptosis by promoting ribosome biosynthesis and translation. SBDS deficiency by vector-based shRNA led to impaired cell expansion of differentiating K562 cells due to accelerated apoptosis and reduced proliferation. Furthermore, the cells showed general reduction of 40S, 60S, 80S ribosomal subunits, loss of polysomes and impaired global translation during differentiation. An upregulation of the pro-apoptotic p53 family member, TAp73, was found in resting SBDS deficient cells; however, not in differentiating cells. These results demonstrate SBDS plays a critical role in erythroid expansion by promoting survival of early erythroid progenitors and in maintaining ribosome biogenesis during erythroid maturation independently of p53 family members.
URI: http://hdl.handle.net/1807/18860
Appears in Collections:Master
Institute of Medical Science - Master theses

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