Analysis of Regulatory Mechanisms of Proplatetet Formation by Small Maf Proteins.
| Project/Area Number |
15590244
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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 |
General medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MOTOHASHI Hozumi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (00282351)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | megakaryocytes / proplatelet formation / small Maf proteins / transgenic mouse / 血小板 / 転写 / 翻訳後修飾 |
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| Research Abstract |
The goal of this study was to clarify the regulatory mechanisms of proplatelet formation through analyang the function of small Maf proteins in megakaryocyte differentiation and maturation and identifying the target genes regulated downstream of small Maf.
(1)Structure-function analysis of small Maf in megakaryocytes
Dimeric transcription factors often consist of one ubiquitous subunit complexed with a more highly restricted partner molecule. MafG is a more common subunit of the MafG:p45 heterodimer, which is an indispensable transcriptional activator mediating proplatelet formation in megakaryocytes. Excess MafG antagonizes the activity of the MafG:p45 heterodimer by forming an inhibitory homodimer, thereby blocking proplatelet formation ; thus MafG both activates and represses transcription depending on its relative abundance. Here we report that MafG is conjugated to SUMO-2/3 in vivo and that SUMOylation-defective MafG, when expressed in megakaryocytes, participates normally in transc
… More
riptional activation, but not in repression. While MafG was found in both heterochromatin and euchromatin, the mutant MafG failed to be localized in heterochromatin. We conclude that SUMOylation is required for MafG-mediated repression and localization to heterochromatin, and thus SUMOylation of the broadly expressed component of this dimeric transcription factor determines one aspect of its transcriptional potential.
(2)Identification of a novel gene regulated downstream of small Maf in megakaryocytes.
In order to clarify the molecular mechanisms operating in the process of proplatelet formation, we searched for the differentially expressed genes between the wild type and small maf mutant megakaryocytes. Among various factors relating to the cytoskeleton, one novel factor called clone 325 was isolated through the subtraction screening. The full length cDNA was obtained from the brain cDNA library, and the deduced amino acid sequence revealed one leucine zipper-like motif but no canonical functional motifs. The clone 325 was highly expressed in the primary megakaryocytes purified from the bone marrow, but its abundance was relatively low in immature hematopoietic cells and in erythroid cells. We disrupted the gene of the clone 325 in mouse and found that the homozygous animals are viable and displayed no abnormality in the cell counts of the peripheral blood. But when megakaryocytes from the bone marrow of the mutant animals were observed, we found that very few cells properly protruded normal proplatelets. This result suggests that the clone 325 is important for the proplatelet formation. Less
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Report
(3 results)
Research Products
(37 results)
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[Journal Article] Evaluation of MafG Interaction with Maf Recognition Element Arrays by Surface Plasmon Resonance Imaging Technique.2004
Author(s)
Kyo, M., Yamamoto, T., Motohashi, H., Kamiya, T., Kuroita, T., Tanaka, T., Engel, J.D., Kawakami, B., Yamamoto, M.
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Journal Title
Genes Cells 9
Pages: 153-164
Description
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[Journal Article] A constitutively active arylhydrocarbon receptor induces growth inhibition of Jurkat T cells through changes in the expression of genes related to apoptosis and cell cycle arrest.2004
Author(s)
Ito, T., Tsukumo, S.I., Suzuki, N., Motohashi, H., Yamamoto, M., Fujii-Kuriyama, Y., Mimura, J., Lin, T.M., Peterson, R.E., Tohyama, C., Nohara, K.
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Journal Title
J.Biol.Chem. 279
Pages: 25204-25210
Description
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[Journal Article] Identification of polymorphisms in the promoter region of the human NRF2 gene.2004
Author(s)
Yamamoto, T., Yoh, K., Kobayashi, A., Ishii, Y., Kure, S., Koyama, A., Sakamoto, T., Sekizawa, K., Motohashi, H^*, Yamamoto, M.(^*co-corresponding author)
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Journal Title
Biochem.Biophys.Res.Commun. 321
Pages: 72-79
Description
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[Journal Article] Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway : Identification of novel gene clusters for cell survival.2003
Author(s)
Kwak, M.K., Wakabayashi, N., Itoh, K., Motohashi, H., Yamamoto, M., Kensler, T.W.
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Journal Title
J.Biol.Chem. 278
Pages: 8135-8145
Description
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[Journal Article] Small Maf compound mutants display CNS neuronal degeneration, aberrant transcription and Bach protein mislocalozation coincident with myoclonus and abnormal startle response.2003
Author(s)
Katsuoka, F., Motohashi, H., Tamagawa, Y., Kure, S., Igarashi, K., Engel, J.D., Yamamoto, M.
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Journal Title
Mol.Cell.Biol. 23
Pages: 1163-1174
Description
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[Journal Article] Distinct response to dioxin in an arylhydrocarbon receptor(AhR)-humanized mouse.2003
Author(s)
Moriguchi, T., Motohashi, H., Hosoya, T., Nakajima, O., Takahashi, S., Ohsako, S., Aoki, Y., Nishimura, N., Tohyama, C., Fujii-Kuriyama, Y., Yamamoto, M.
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Journal Title
Proc.Natl.Acad.Sci.USA 100
Pages: 5652-5657
Description
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[Journal Article] Identification and characterization of two types of erythroid progenitors that express GATA-1 at distinct levels.2003
Author(s)
Suzuki, N., Suwabe, N., Ohneda, O., Obara, N., Imagawa, S., Pan, X., Motohashi.H., Yamamoto, M.
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Journal Title
Blood 102
Pages: 3575-3583
Description
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[Journal Article] Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation.2003
Author(s)
Wakabayashi, N., Itoh, K., Wakbayashi, J., Motohashi, H., Noda, S., Takahashi, S., Imakado, S., Kotsuji, T., Otsukua, F., Roop, D.R., Harada, T., Engel, J.D., Yamamoto, M.
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Journal Title
Nat.Genet. 35
Pages: 238-245
Description
「研究成果報告書概要(欧文)」より
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[Publications] Noda, S., Harada, N., Hida, A., Fujii- Kuriyama, Y., Motohashi, H^*., Yamamoto M: "Gene expression of detoxifying enzymes in AhR and Nrf2 compound null mutant mouse. (^*Corresponding author)"Biochem.Biophys.Res.Commun.. 303. 105-111 (2003)
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[Publications] Suzuki, N., Suwabe, N., Ohneda, O., Obara, N., Imagawa, S., Pan, X., Motohashi.H., Yamamoto, M.: "Identification and characterization of two types of erythroid progenitors that express GATA-1 at distinct levels"Blood. 102. 3575-3583 (2003)
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