| RRC ID |
12235
|
| 著者 |
Yamaguchi M, Fujimura K, Kanegane H, Toga-Yamaguchi H, Chopra R, Okamura N.
|
| タイトル |
Mislocalization or low expression of mutated Shwachman-Bodian-Diamond syndrome protein.
|
| ジャーナル |
Int J Hematol
|
| Abstract |
Shwachman-Diamond syndrome (SDS) is an autosomal-recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. Mutations in the SBDS gene are identified in most patients with SDS. Recent studies have shown that SBDS is involved in ribosome biogenesis and is localized to the nucleolus. The significance of cellular localization in SBDS is unknown, particularly as SBDS does not exhibit canonical nuclear localization signals. In this study, we have constructed wild-type deletion mutants of the critical domains and disease-associated mutants of the SBDS gene. These constructs were expressed in HeLa cells to explore the subcellular distribution of normal and mutant proteins. Wild-type SBDS was detected in the nucleus. However, constructs lacking N-terminal Domain I and two disease-associated mutants (C31W and N34I) failed to localize SBDS to the nucleus. Moreover, the amount of mutated SBDS protein was decreased. When N-terminal Domain I was overexpressed in HeLa cells, the localization of endogenous SBDS protein was changed from nuclei to cytosolic fraction. These data indicate that the N-terminal Domain I is responsible for nuclear localization. Furthermore, low expression of SBDS, as exhibited in some of the disease-associated mutants, may be associated with the pathogenesis of SDS.
|
| 巻・号 |
94(1)
|
| ページ |
54-62
|
| 公開日 |
2011-7-1
|
| DOI |
10.1007/s12185-011-0880-1
|
| PII |
10.1007/s12185-011-0880-1
|
| PMID |
21660439
|
| MeSH |
Active Transport, Cell Nucleus
Bone Marrow Diseases / etiology*
Bone Marrow Diseases / genetics
Exocrine Pancreatic Insufficiency / etiology*
Exocrine Pancreatic Insufficiency / genetics
Gene Expression
HeLa Cells
Humans
Lipomatosis / etiology*
Lipomatosis / genetics
Mutant Proteins / metabolism*
Nuclear Proteins
Proteins / genetics
Proteins / metabolism*
Shwachman-Diamond Syndrome
|
| IF |
2.245
|
| 引用数 |
1
|
|
WOS 分野
|
HEMATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
277-LCL(RCB2283) |
