2004 Fiscal Year Final Research Report Summary
The effects of phosphorylation and acetylation-mediated modification on functional activity of PU.12
| Project/Area Number |
15591032
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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 |
Hematology
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| Research Institution | Sasaki institute |
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Principal Investigator |
NEGISHI Fumiko Sasaki institute, Cell Genrtics, Researcher, 細胞遺伝部, 主任研究員 (40177902)
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| Co-Investigator(Kenkyū-buntansha) |
山田 俊幸 (財)佐々木研究所, 細胞遺伝部, 主任研究員 (20183981)
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| Project Period (FY) |
2003 – 2004
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| Keywords | phosphorylation / acetylation / PU.1 / hematonietic cell differentiation / leukemia |
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| Research Abstract |
Physiological activity of transcription factors can be changed by switching its association with coactivators and corepressors. Recently, acetylation-mediated modification, in addition of phosphorylation, has been shown to regulate transcriptional activities of a number of regulatory factors. PU.1 is a hematopoietic-specific Ets family transcription factor which is required for development of some lymphoid and myeloid lineages. We previously found that PU.1 functions as a positive or negative transcription factor through complex formation with CBP or HDAC1/mSin3A/MeCP2. To find what modification of PU.1 is responsible for switching its association with cofactors, we investigated whether acetylation regulate physical and functional activity of PU.1. PU.1 was in vivo acetylated and its repressor but not activator activity was reduced when the putative acetylation motifs resemble for a critical factor for erythroid cells development, GATA-1 was mutated. This acetylation mutant cooperated with CBP in a similar extent to wild type PU.1, but insufficiently interacted GATA-1 and mSin3A. Interestingly, overexpression of PU.1 having mutation within the acetylation motifs did not induce block cell growth and differentiation, and induce apoptosis in MEL cells. Taken together, our data suggest that acetylation might regulate repressor activity of PU.1 responsible for cell differentiation and apoptosis.
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Research Products
(7 results)
