ライフサイエンスコーパス: SBDS

1 SBDS colocalized with the mitotic spindle in control pri

2 SBDS encodes a highly conserved protein of unknown funct

3 SBDS encodes a highly conserved protein previously impli

4 SBDS forms a protein complex with nucleophosmin, a multi

5 SBDS localization was cell-cycle dependent, with nucleol

6 SBDS loss results in both hematopoietic cell-intrinsic d

7 SBDS migrates together with the 60S large ribosomal subu

8 SBDS nucleolar localization was intact in SD101 and DF26

9 SBDS synthesis increased in hematopoietic cells, whereas

10 SBDS therefore appears to be required for normal pancrea

11 SBDS-deficient hESCs and iPSCs manifest deficits in exoc

12 and candidate gene sequencing in additional SBDS-negative SDS cases or molecularly undiagnosed IBMFS

13 In summary, we demonstrate an SBDS-dependent ribosome maturation defect in SDS patient

14 ccharomyces cerevisiae orthologs of CLN3 and SBDS.

15 EFL1 and SBDS, the protein mutated in the Shwachman-Diamond syndr

16 Thus, we propose that Sdo1p and SBDS work to regulate Btn1p and CLN3, respectively.

17 in the Shwachman-Diamond syndrome-associated SBDS gene with concurrent TP53 mutations and a poor prog

18 ontrols, and no physical interaction between SBDS protein and telomerase complex components (TERT or

19 for their age, and in SDS patients with both SBDS alleles affected further analyzed, granulocytes' te

20 granulocytic differentiation, is altered by SBDS mutations or knockdown.

21 we report heterozygosity for the 258 + 2 T>C SBDS gene mutation previously identified in SDS patients

22 pose that heterozygosity for the 258 + 2 T>C SBDS mutation predisposes to AA by accelerating telomere

23 kocytes of SDS patients with the most common SBDS mutations, consistent with a loss-of-function mecha

24 In contrast, SBDS protein was expressed at normal levels in SDS patie

25 al association defect, while patient-derived SBDS point mutants only partially improved subunit assoc

26 ies (TERC, TERT, RTEL1), ribosome disorders (SBDS, DNAJC21, RPL5), and DNA repair deficiency (LIG4).

27 The release factors SBDS and EFL1-both mutated in the leukemia predispositio

28 Our findings establish a direct role for SBDS and EFL1 in catalyzing the translational activation

29 Data from SBDS orthologs suggest that SBDS may play a role in ribo

30 s in Shwachman-Bodian-Diamond syndrome gene (SBDS), which encodes a ribosome assembly factor.

31 We show that germline SBDS deficiency establishes a fitness constraint that dr

32 Human SBDS is enriched in the nucleolus, the major cellular si

33 Mutations in the human SBDS (Shwachman-Bodian-Diamond syndrome) gene are the mo

34 hromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively.

35 Full-length SBDS protein was not detected in leukocytes of SDS patie

36 with SDS exhibited no detectable full-length SBDS protein.

37 sembly and protein synthesis across multiple SBDS-deficient species including yeast, Dictyostelium an

38 These data confirm the absence of SBDS mutations in this subgroup of patients and suggest

39 The presence (or absence) of SBDS mutations may define subgroups of patients with SDS

40 Telomerase activity of SBDS-deficient patients' lymphocytes was comparable with

41 did not correct the hematopoietic defect of SBDS-deficient cells.

42 ibosomal maturation due to the deficiency of SBDS and the inability to evict the antiassociation fact

43 Similarly, depletion of SBDS by siRNA in human skin fibroblasts resulted in incr

44 Elucidating the molecular function of SBDS will provide important insights into how defects in

45 Length of telomeres in granulocytes of SBDS heterozygous patients was short for their age, and

46 stem cell models of SDS through knockdown of SBDS in human embryonic stem cells (hESCs) and generatio

47 Patient SD101 expressed low levels of SBDS protein harboring an R169C missense mutation.

48 ene mutations, expressed wild-type levels of SBDS protein to add further support to the growing body

49 in the SBDS gene, resulting in low levels of SBDS protein.

50 ce donor mutation, expressed scant levels of SBDS protein.

51 The intranucleolar localization of SBDS provides further supportive evidence for its postul

52 ized by partial rather than complete loss of SBDS expression, we interrogated SDS patient cells for d

53 sturbance of specific translation by loss of SBDS function may contribute to the development of the S

54 It is unknown, however, if loss of SBDS functionality affects the translation of specific m

55 Loss of SBDS is not associated with a discrete block in rRNA mat

56 Recent studies show that mutations of SBDS, a gene of unknown function, are present in the maj

57 g SDS had compound heterozygous mutations of SBDS.

58 binding to EFL1 alone and in the presence of SBDS using fluorescence stopped-flow spectroscopy.

59 variants reveals that the essential role of SBDS is to tightly couple GTP hydrolysis by EFL1 on the

60 Recombinant SBDS protein stabilized microtubules in vitro.

61 ung and had a poor outcome; they had reduced SBDS expression but no evidence of the pancreatic exocri

62 atants, which could be reversed by restoring SBDS protein expression through transgene rescue or by s

63 imary and secondary endpoints were restoring SBDS protein levels in hematopoietic cells and improving

64 ns in the Shwachman-Bodian-Diamond syndrome (SBDS) gene are found in the majority of patients, but th

65 the human Shwachman-Bodian-Diamond syndrome (SBDS) gene cause defective ribosome assembly and are ass

66 ns in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene cause Shwachman-Diamond Syndrome (SDS), a rar

67 ns in the Shwachman-Bodian Diamond syndrome (SBDS) gene, which encodes a factor involved in ribosome

68 ns in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene.

69 ns in the Shwachman-Bodian-Diamond syndrome (SBDS) gene.

70 ns in the Shwachman Bodian Diamond syndrome (SBDS) gene.

71 acterized Shwachman-Bodian-Diamond syndrome (SBDS) protein expression and intracellular localization

72 conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein.

73 DA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and

74 n mutated in the Shwachman-Diamond syndrome (SBDS), release the anti-association factor eIF6 from the

75 The gene for this syndrome, SBDS, encodes a highly conserved novel protein.

76 in a translationally inactive state and that SBDS and EFL1 are the minimal components required to rec

77 917-929) establish that SBDS functions in ribosome synthesis by promoting the re

78 Current studies indicate that SBDS functions in 60S large ribosomal subunit maturation

79 Here we report that SBDS nucleolar localization is dependent on active rRNA

80 ubunits from Sbds-deleted mice, we show that SBDS and the GTPase elongation factor-like 1 (EFL1) dire

81 We show that SBDS function is specifically required for efficient tra

82 hoblasts, and skin fibroblasts, we show that SBDS stabilized the mitotic spindle to prevent genomic i

83 Data from SBDS orthologs suggest that SBDS may play a role in ribosome biogenesis or RNA proce

84 The SBDS protein is important for ribosome maturation and th

85 The SBDS protein was detected in both the nucleus and the cy

86 data support a multifunctional role for the SBDS protein.

87 Mutations in the SBDS gene are identified in most patients with SDS.

88 Deficiencies in the SBDS gene result in Shwachman-Diamond syndrome (SDS), an

89 s with a genetic (biallelic mutations in the SBDS gene) or clinical diagnosis (cytopenias and pancrea

90 S patients harbor biallelic mutations in the SBDS gene, resulting in low levels of SBDS protein.

91 Biallelic mutations in the SBDS or EFL1 genes in SDS impair release of the anti-ass

92 dicate a requirement for the ortholog of the SBDS (Shwachman-Bodian-Diamond syndrome) gene that is mu

93 s caused by mutations in both alleles of the SBDS gene, which encodes a protein of unknown function.

94 behavior was observed in the presence of the SBDS protein irrespective of the guanine nucleotide eval

95 patients, but the molecular function of the SBDS protein product remains unclear.

96 vents the nucleotide exchange regulation the SBDS exerts on EFL1.

97 ta from nonhuman models demonstrate that the SBDS protein facilitates the release of eIF6, a factor t

98 at modulation of ribosome maturation through SBDS protein can be helpful for manipulating cell stemne

99 Thus, SBDS acts as a guanine nucleotide exchange factor (GEF)

100 Association of EFL1 to SBDS did not modify the affinity for GTP but dramaticall

101 Introduction of a wild-type SBDS cDNA into SDS patient cells corrected the ribosomal

102 The addition of wild-type SBDS complements the actinomycin D hypersensitivity of S

103 We demonstrate that CLN3 interacts with SBDS, the protein mutated in Shwachman-Bodian-Diamond sy

104 ere even shorter, correlating in length with SBDS expression.

105 sed at normal levels in SDS patients without SBDS mutations.

106 Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the