Kyushu University · Medicine
Professor Takeshi Uchiumi's research lab focuses on molecular mechanisms underlying drug resistance, cellular transport, and gene regulation in human diseases, particularly cancer and hereditary disorders. The lab investigates ABC transporters such as MDR1 and MRP2, exploring their regulation, trafficking, and role in multidrug resistance and Dubin-Johnson syndrome. Additionally, the lab examines key regulatory proteins like YB-1 and PLK in cell cycle control and development, as well as mitochondrial GTP-binding proteins like ERAL1 in translation and organelle function. Their work integrates molecular biology, cell biology, and genetics to understand disease pathogenesis and identify potential therapeutic targets.
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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