CHARACTERIZATION OF A NEW RETINAL AUTOANTIGEN GENE CORRESPONDING WITH CANCER-ASSOCIATED RETINOPATHY
| Project/Area Number |
13671829
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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 |
Ophthalmology
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
KIKUCHI Takanobu RESEARCH CENTER FOR INSTRUMENTAL ANALYSIS, ASSOCIATE PROFESSOR, 機器分析センター, 助教授 (50177797)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Koichi OPHTHALMOLOGY, ASISTANT PROFESSOR, 医学部附属病院, 講師 (70262730)
YOSIMURA Nagahisa OPHTHALMOLOGY, PROFESSOR, 医学部, 教授 (70211662)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Cancer-associated retinopathy / autoantibody / retinal antigen / PTB-like protein / RNA binding protein / 抗原決定部位 / RNA結合タンパク / PTBLP遺伝子 |
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| Research Abstract |
(1) Human homologue of polypyrimidine tract binding protein (PTB), a possible autoantigen for cancer-associated retinopathy (CAR), was isolated from a human retinal cDNA library. This homologue, named PTB-like protein (PTBLP), encodes a 532 amino acid residue protein and has four RNA recognition motifs (RRMs). The third and fourth RRMs are required for RNA binding ability. CAR serum recognized the PTBLP, the antigenic determinant of the PTBLP was localized within 12 amino acids of the C-terminal region. The sequence of the peptide was included in the fourth RRM sequence. Autoantibodies in the sera of the patients with paraneoplastic neurologic disorders react to a variety of neuron specific proteins. These proteins can be classified into three groups : (1) cell surface protein, e.g., voltage-gated calcium channels, (2) cytosolic proteins, e.g., recoverin and TULP1 ; and (3) nuclear RNA binding proteins, e.g., Hu-family proteins containing RRM domain and NOVA protein containing KH domai
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n. The PTBLP is a new member of the third group. This study expands the understanding of the pathogenesis of paraneoplastic disorders with antibodies against neuronal RNA binding proteins.
(2) We have studied whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of NGF-induced neuronal differentiation of PC12 cells, PTBLP-L (long form containing four RRMs) was down-regulated whereas PTBLP-S (short form containing only two RRMs in the N-terminal region) was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L. Less
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Report
(3 results)
Research Products
(7 results)
