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| STAFF |
Professor : Naomi KITAMURA, Associate Prof. : Masayuki KOMADA
Assistant Prof. : Kiminori DENDA, Toshiaki TANAKA |
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| Website of the KITAMURA_KOMADA Lab >> http://www.kitamura-komada-lab.bio.titech.ac.jp/ |
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| Research |
The regulation of cell proliferation plays important roles in embryonic development and morphogenesis, as well as in tissue repair and regeneration in mature individuals. Breakdown of this mechanism is also the cause of cell proliferative disorders such as cancer. At Kitamura-Komada Laboratory we are conducting research into the mechanisms of cell proliferation control, focusing primarily on signalling within the cell carried out by growth factors, down-regulation of growth factor receptors and the molecular pathways involved in cytokinesis.
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| HGF plays an important role in regulating cell proliferation during morphogenesis and tissue repair. We are investigating what mechanisms are involved in transmitting signals inside the cell and in regulating cell proliferation once HGF has interacted with the cell surface receptor, c-Met. Mutations in the c-Met gene have recently been identified as the cause of the disease, hereditary papillary renal cell cancer (HPRCC). Consequently, our research has an important role to play in the identification of the mechanisms involved in cells becoming cancerous and in the development of anticancer medications that target signalling molecules. |
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| In moving from the process of proliferation to that of differentiation, cells must exit the proliferation cycle and stop at the G1/G0 phase of the cell cycle. Moreover, at G1 cells take on external information and can differentiate in response to their surroundings for the first time. At Kitamura-Komada Laboratory we are utilising clawed frog embryos and mouse ES cells as the research models for our analysis of the molecular pathways of G1 phase change seen at the time of cell differentiation induction in order to investigate the mechanisms at play when cells switch over from proliferation to differentiation. |
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| Growth factor receptors on the cell surface are activated when growth factor binds to them. Activated receptors are quickly taken into the cell and delivered through endosomes to lysosomes for degradation. This mechanism of receptor down-regulation is important in regulating proliferation as it disposes of the activated receptor and prevents excessive cell proliferation. Once activated, growth factor receptors undergo ubiquitination, and this modification serves as the signal for their delivery to the lysosome. Here at Kitamura-Komada Laboratory we are conducting cell biological analysis on cultured human cells and analysis of knock-out mice in order to study the molecular pathways involved in the down-regulation of growth factor receptors through ubiquitination and the opposing process, deubiquitination. In some cancers, there is over-expression of growth factor receptors and they are constantly activated. Our research aims to identify the underlying mechanism of these cancers and use the relevant proteins as the molecular target for the development of carcinostatic drugs.
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Cytokinesis is a dynamic cellular process whereby a cell is split into two daughter cells following mitosis. It is regulated by a range of molecular mechanisms such as signal transduction, cytoskeletal dynamics and membrane trafficking. We have discovered that in cytokinesis, spatio-temporal protein ubiquitination occurs at the central spindle, a bundle of microtubules formed between separating daughter cell DNAs. In an attempt to uncover the whole picture of the molecular mechanisms underlying cytokinesis, we are now conducting cell biological analysis of cultured human cells to investigate the role of ubiquitination and deubiquitination in cytokinesis. Defects in cytokinesis are associated with the emergence of multinucleate cells, which are known to change toaneuploid cells that eventually become cancer cells. Thus, our research in this area is also extremely important for identifying the underlying mechanisms of cancer. |
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| Papers |
| 1) |
M. Maemura, A.Yoshimoto, Y,Tsukada, Y.Morishita，K.Miyazawa, T.Tanaka, and N. Kitamura:lnhibitory effect of c−Met mutants on the formation of branching
tubuIes by a porcine aortic endothelial cell line. Cancer Sci.97,1343−1350(2006) |
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Y.Uemoto, S.Suzuki, N.Terada, N. Ohno, S.0hno, S.Yamanaka, M.Komada：Specific role of the truncated betalV-spectrin Sigma6 in sodium channel clustening at axon initial segments and nodes of Ranvier,J.Biol.Chem.282,6548-6555(2007) |
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E.Mizuno, N.Kitamura, M.Komada： 14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase.Exp. Cell Res.313,
3624-3634(2007) |
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A.Mukai, E.Mizuno, K.Kobayashj, M.Matsumoto,K.I.Nakayama, N.Kitamura, M.Komada：Dynamic reguIation of ubiquityration and deubiquitylation at the central spindle during cytokinesis. J.Cell Sci. 121, 1325-1333(2008) |
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E. Shirako, N.Hirayama, Y.Tskada, T.Tanaka, and N.Kitamura: Up-regulation of p21CIP1 expression mediated by ERK-dependent and-independent pathways contributes to hepatocyte growth factor-induced inhibition of HepG2 hepatoma cell proliferation. J. Cell. Biochem. 104,176-188(2008) |
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A. Kondo, N.Hirayama, Y.Sugjto, M.Shono, T.tanaka, and N.Kitamura：Coupling of Grb2 to Gab1 mediates hepatocyte growth factor-induced high lntensity ERK signalrequired for inhibition of HepG2 hepatoma cell proliferation. J.Biol. Chem. 283, 1428-1436(2008) |
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