|
|
Blood, 1 September 2007, Vol. 110, No. 5, pp. 1458-1465.
Prepublished online as a Blood First Edition Paper on May 2, 2007; DOI 10.1182/blood-2007-02-075184.
 Previous Article | Next Article 
Submitted February 20, 2007
Accepted April 30, 2007
The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA
Karthik A Ganapathi, Karyn M Austin, Chung-Sheng Lee, Anusha Dias, Maggie M Malsch, Robin Reed, and Akiko Shimamura*
Dept of Pediatric Hematology, Children's Hospital Boston, Department of Pediatric Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, United States
Department of Cell Biology, Harvard Medical School, Boston, MA, United States
* Corresponding author; email: akiko.shimamura{at}childrens.harvard.edu.
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic dysfunction and leukemia predisposition. Mutations in the SBDS gene are identified in the majority of patients with SDS. SBDS encodes a highly conserved protein of unknown function. Data from SBDS orthologues suggest that SBDS may play a role in ribosome biogenesis or RNA processing. Human SBDS is enriched in the nucleolus, the major cellular site of ribosome biogenesis. Here we report that SBDS nucleolar localization is dependent on active rRNA transcription. Cells from patients with SDS or Diamond-Blackfan anemia are hypersensitive to low doses of actinomycin D, an inhibitor of rRNA transcription. The addition of wildtype SBDS complements the actinomycin D hypersensitivity of SDS patient cells. SBDS migrates together with the 60S large ribosomal subunit in sucrose gradients and co-precipitates with 28S ribosomal RNA (rRNA). Loss of SBDS is not associated with a discrete block in rRNA maturation or with decreased levels of the 60S ribosomal subunit. SBDS forms a protein complex with nucleophosmin, a multifunctional protein implicated in ribosome biogenesis and leukemogenesis. Our studies support the addition of SDS to the growing list of human bone marrow failure syndromes involving the ribosome.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Connecting ribosomes with bone marrow failure
- Stefan Karlsson
Blood 2007 110: 1402.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
H. L. Ball, B. Zhang, J. J. Riches, R. Gandhi, J. Li, J. M. Rommens, and J. S. Myers
Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in cellular stress responses
Hum. Mol. Genet.,
October 1, 2009;
18(19):
3684 - 3695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Albrecht, S. W. Gorges, D. M. Styne, and A. A. Bremer
Shwachman-Diamond Syndrome Presenting as Hypoglycemia
Clinical Pediatrics,
March 1, 2009;
48(2):
212 - 214.
[PDF]
|
|
|
|
|
|
|
C. Orelio and T. W. Kuijpers
Shwachman-Diamond syndrome neutrophils have altered chemoattractant-induced F-actin polymerization and polarization characteristics
Haematologica,
March 1, 2009;
94(3):
409 - 413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Calado and N. S. Young
Telomere maintenance and human bone marrow failure
Blood,
May 1, 2008;
111(9):
4446 - 4455.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Rujkijyanont, K.-i. Watanabe, C. Ambekar, H. Wang, A. Schimmer, J. Beyene, and Y. Dror
SBDS-deficient cells undergo accelerated apoptosis through the Fas-pathway
Haematologica,
March 1, 2008;
93(3):
363 - 371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Rawls, A. D. Gregory, J. R. Woloszynek, F. Liu, and D. C. Link
Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential
Blood,
October 1, 2007;
110(7):
2414 - 2422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
