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 therefore appears to be required for normal pancrea

10 SBDS-deficient hESCs and iPSCs manifest deficits in exoc

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

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

13 ccharomyces cerevisiae orthologs of CLN3 and SBDS.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

50 g SDS had compound heterozygous mutations of SBDS.

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

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

53 Recombinant SBDS protein stabilized microtubules in vitro.

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

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

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

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

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

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

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

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

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

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

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

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

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

67 917-929) establish that SBDS functions in ribosome synthesis by promoting the re

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

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

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

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

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

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

74 The SBDS protein is important for ribosome maturation and th

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

76 data support a multifunctional role for the SBDS protein.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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