九州大学 · 医学
UCHIUMI教授の研究室は、膜タンパク質の機能制御とその遺伝子発現機構に焦点を当てており、特に多剤耐性関連タンパク質(MDR1、MRP2)や細胞周期制御に関与するキナーゼ(PLK)の発現調節機構を分子遺伝学的手法を用いて解明しています。また、YB-1 や ERAL1 といった転写・翻訳調節因子の機能とその発生・細胞内局在における役割についても、遺伝子ノックアウトやRNA干渉を用いた解析を進めています。特に、がんや先天性疾患に関連するタンパク質の機能異常とその細胞内メカニズムの解明が中心的な研究テーマです。
Figures are computed from collected data and may differ slightly.
The multidrug resistance 1 (MDR1) gene encodes a M(r) 170,000 membrane glycoprotein termed P-glycoprotein, which catalyzes the energy-dependent efflux of multiple anticancer agents. We investigated the activation of the MDR1 gene promoter by UV light irradiation in human cancer KB cells after both transient and stable transfection assays of the MDR1 promoter fused to the chloramphenicol acetyltransferase (CAT) gene. Following exposure to UV irradiation, CAT gene expression was about 20-fold incr
Plk (polo-like kinase) is a serine-threonine kinase that appears to function in mitotic control in mammalian cells. We demonstrated previously that PLK mRNA expression is low at the G1-S transition, increases during S phase, and is maximally expressed during G2-M. In the present study, we have cloned the human PLK gene and analyzed the structure and function of 2 kilobases of its 5'-flanking region. Using synchronized cultures of HeLa cells transfected with PLK promoter/luciferase constructs, we
The eukaryotic Y-box-binding protein-1 (YB-1) is involved in the transcriptional and translational control of many biological processes, including cell proliferation. In clinical studies, the cellular level of YB-1 closely correlates with tumor growth and prognosis. To understand the role of YB-1 in vivo, especially in the developmental process, we generated YB-1 knock-out mice, which are embryonic lethal and exhibit exencephaly associated with abnormal patterns of cell proliferation within the
Dubin-Johnson syndrome (DJS) is a hereditary disease characterized by hyperbilirubinemia. We investigated the consequences of 2 missense mutations, R768W and Q1382R, of nucleotide-binding domains (NBDs) of the multidrug resistance protein 2 (MRP2; ABCC2) that were previously identified in patients with DJS. Pulse chase analysis revealed that the precursor form of the wild-type and Q1382R MRP2 were converted to the mature form, which is resistant to endoglycosidase H (Endo H) in about 60 minutes.
ERAL1, a homologue of Era protein in Escherichia coli, is a member of conserved GTP-binding proteins with RNA-binding activity. Depletion of prokaryotic Era inhibits cell division without affecting chromosome segregation. Previously, we isolated ERAL1 protein as one of proteins which were associated with mitochondrial transcription factor A by using immunoprecipitation. In this study, we analysed the localization and function of ERAL1 in mammalian cells. ERAL1 was localized in mitochondrial matr
The human multidrug resistance protein 2 (MRP2), also termed as the canalicular multispecific organic anion transporter (cMOAT), is a member of the adenosine triphosphate-binding cassette transporter superfamily. In the liver, MRP2 mediates the multispecific efflux of various types of organic anions, including glucuronate, sulfate, and glutathione conjugates, across the canalicular hepatocyte membrane to the bile. To investigate how the MRP2 gene is expressed in liver cells, the 5'-flanking regi
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