1998 Fiscal Year Final Research Report Summary
Regulation by PU.1 of CYBB Expression
| Project/Area Number |
09671123
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
NAKAMURA Michio Institute of Tropical Medicine, Nagasaki University, Dept.of Host-defense Biochemistry Professor, 熱帯医学研究所, 教授 (30091276)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Shoichi Institute of Tropical Medicine, Nagasaki University, Dept.of Host-defense Bioche, 熱帯医学研究所, 助手 (40253695)
KUMATORI Atsushi Institute of Tropical Medicine, Nagasaki University, Dept.of Host-defense Bioche, 熱帯医学研究所, 講師 (60244092)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | CYBB / PU.1 / gp91phox / HAF-1 / transcription / phagocyte / NADPH oxidase / chronic granulomatous disease |
|---|
| Research Abstract |
Phagocyte NADPH oxidase makes superoxide anion which is essential for microbial killing and is expressed on the surface of mature neutrophils. eosinophils, monocytes/macrophages and B lymphocytes. It is a multi-component cnzymes and contains gp9lphox, a flavo-heme protein, which is encoded in CYBB on X chromosome. Abnormalities of this gene, therefore, occupy more than 70% of NADPH oxidase deficiency called chronic granulomatous disease. We rcccntly discovered a CGD patient with phenotypically normal eosinophils, and suggested certain mechnisrn particular to neutrophils, monocytes and B lymphocytes : Analysis of promoter sequence revealed a C to T point mutation at -53 of CYBB Electrophoresis mobility shift assays exhibited PU.1 and hematopoietic associated factor-l(HAF-1) as the binding proteins whose binding is sensitive to this mutation. We discovered -56G and -50G mutations to fail in binding to only HAF-1 and PU.1, respectively. The latter mutation but not the former one decreased the promoter activity as -53T mutation. Accordingly these results indicate PU.l, but not HAF-1, to be essential for the expression of CYBB in neutrophils, monocytes, and B lymphocytes. Interaction of PU.1 with transcriptional modulators are now under experiments. PU.1 is also detectable in eosinophils, and may have a significant role in the cells for CYBB activation, even if it is not essential. In addition, we found GATA-3 to be ensinophil-specific repressor of CYBB.
|
Research Products
(8 results)
-
-
-
-
-
[Publications] S.Suzuki, A.Kumatori, I-A.Haagen, Y.Fujii, M.A.Sadat, H.L.Jun, Y.Tsuji, D.Roos, and M.Nakamura: "PU.1 as an essential activator for the expression of gp91phox gene in human peripheral neutrophils, monocytes, and B lymphocytes" Proc.Natl.Acad.Sci.USA.95-11. 6085-6090 (1998)
Description
「研究成果報告書概要(欧文)」より
-
-
-
