Reserch

Home  >  Research  >  Institute for Molecular and Cellular Regulation

• Research
  • Faculty of Education
  • Faculty of Social and Information Studies
  • Faculty of Medicine
    - School of Medicine
    - School of Health Sciences
  • School of Science and Technology
  • Institute for Molecular and Cellular Regulation
  • Heavy Ion Medical Center
  • Gunma University Hospital

II. KUBOHARA GROUP

Cellular slime molds are soil microorganisms belonging to a kingdom different from fungi that produce many pharmacologically active compounds including polyketides. Thus, cellular slime molds are expected to be a novel resource for lead compounds in the field of pharmacology and medicine. On the other hand, Dictyostelium discoideum (Fig. 4), a cellular slime mold, is a well-studied model organism in the fields of cell and developmental biology. Our research on cellular slime molds extends over basic cell biology and pharmacology/medicine.

---

CURRENT PROJECTS

(1) Analysis of the mechanisms of cell differentiation and chemotaxis of D. discoideum.

Differentiation-inducing factor-1, -2, and -3 (DIFs 1–3) (Fig. 5) were originally identified as the differentiation-inducing factors of stalk cells in D. discoideum. Recently, DIF-1 and DIF-2 were found to function also as negative and positive modulators of chemotactic cell movement, respectively, in this organism. However, the precise mechanisms underlying the actions of DIF-1 and DIF-2 remain to be elucidated, and there have been no receptors identified for DIFs. We are now searching for DIF receptors and elucidating the mechanisms of the actions of DIFs.

(2) Study on pharmacological activities of DIFs and exploitation of novel drugs

Among many pharmacologically active compounds found in cellular slime molds so far, DIFs (members of the polyketide family) are the most promising and well-studied leads for the development of novel drugs. DIF-3 and its derivatives possess strong anti-tumor activity, while DIF-1 promotes glucose uptake in non-transformed mammalian cells in vitro. In addition, some other DIF derivatives control IL-2 production in T cells. We are now elucidating the mechanisms of the actions of DIF-like molecules in mammalian cells and tying to develop DIF-derived drugs against cancer, obesity and diabetes, etc.

---

RECENT MAIN PUBLICATIONS

1. Kubohara Y, Kikuchi H, Matsuo Y, Oshima Y, & Homma Y. Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum. PLOS ONE 2013; 8: e72118.
2. Nakajima-Shimada J, Hatabu T, Hosoi Y, Onizuka Y, Kikuchi H, Oshima Y, & Kubohara Y. Derivatives of Dictyostelium discoideum differentiation-inducing factor-3 suppress the activities of Trypanosoma cruzi in vitro and in vivo. Biochem. Pharmacol. 2013; 85: 1603-1610.
3. Luciani M-F, Giusti C, Harms B, Oshima Y, Kikuchi H, Kubohara Y, & Golstein P. Atg1 allows second-signalled autophagic cell death in Dictyostelium. Autophagy 2011; 7: 501-508.
4. Kuwayama H & Kubohara Y. Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis. PLOS ONE 2009; 4: e6658.