Studies of nucleolin, a shuttle protein between the nucleus, cytoplasm, and cell surface
| Project/Area Number |
18590076
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
HIRANO Kazuya Tokyo University of Pharmacy and Life Science, SCHOOL OF PHARMACY, LECTURER (80251221)
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| Co-Investigator(Kenkyū-buntansha) |
BEPPU Masatoshi TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCES, SCHOOL OF PHARMACY, SCHOOL OF PHARMACY, PROFESSOR (60114633)
MIKI Yuichi TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCES, SCHOOL OF PHARMACY, RESEARCH ASSOCIATE (20366420)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,930,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | NUCLEOLIN / SHUTTLE PROTEIN / タンパク質 |
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| Research Abstract |
We previously found that induction of apoptosis in human Jurkat T cells results in transient capping of CD43 glycoprotein, at the stage earlier than that of phosphatidylserine exposure, and its sialylpolylactosaminyl chains serve as ligands for phagocytic recognition by macrophages. We have also shown that cell-surface nucleolin is involved in the recognition of sialylpolylactosaminyl chains cluster of early apoptotic cells.
Nucleolin is a multifunctional shuttling protein present in nucleus, cytoplasm, and on the surface of some types of cells. Human nucleolin is composed of 710 amino acids and it's amino-terminal third contains alternating acidic and basic domains, its middle section contains four consensus RNA-binding domains (RBDs), and its carboxy-terminus contains a glycine/arginine-rich domain.
In order to examine how cell-surface nucleolin is located on the cell surface, where it might be accessible to function as a receptor for apoptotic cells, the binding of various deletion constructs of recombinant nucleolins produced in E. coli (rNUCs) to macrophages were examined. Flowcytometric analysis using rNUCs revealed that the macrophage-binding site is located in the center region of nucleolin, containing RBDs. Previous studies suggested that some residues within the 295-302 of nucleolin are likely to be required for the recognition of early apoptotic cells.
These results suggest that nucleolin binds to sialylpolylactosaminyl chains cluster on early apoptotic cells via some residues within the 295-302, whereas it interacts with macrophage via RBDs, then promoting macrophage recognition of early apoptotic cells as a bridging molecule.
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Report
(3 results)
Research Products
(29 results)
