The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Professor Mutsuhiro Takekawa's research lab focuses on cellular stress responses, particularly the molecular mechanisms underlying stress signaling pathways such as the MAPK cascade and stress granule dynamics. The lab investigates how cells sense and transduce environmental stresses—like oxidative stress, ER stress, and DNA damage—into intracellular signals that determine cell fate decisions between survival and apoptosis. Key areas of interest include the redox regulation of signaling molecules such as MTK1 (MEKK4), the role of post-translational modifications like O-GlcNAcylation in stress response, and the pathophysiology of stress-related diseases such as hypereosinophilic syndrome. The lab also develops innovative biochemical methods for detecting and quantifying protein modifications, including lectin-based separation techniques for O-GlcNAcylated proteins.
Figures are computed from collected data and may differ slightly.
Cytoplasmic stress granules (SGs) are multimolecular aggregates of stalled translation pre-initiation complexes that prevent the accumulation of misfolded proteins, and that are formed in response to certain types of stress including ER stress. SG formation contributes to cell survival not only by suppressing translation but also by sequestering some apoptosis regulatory factors. Because cells can be exposed to various stresses simultaneously in vivo, the regulation of SG assembly under multiple
The mitogen-activated protein kinase (MAPK) module, composed of a MAPK, a MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK), is a cellular signaling device that is conserved throughout the eukaryotic world. In mammalian cells, various extracellular stresses activate two major subfamilies of MAPKs, namely, the Jun N-terminal kinases and the p38/stress-activated MAPK (SAPK). MTK1 (also called MEKK4) is a stress-responsive MAPKKK that is bound to and activated by the stress-inducible GADD45 family o
Cells respond to oxidative stress by inducing intracellular signaling, including stress-activated p38 and JNK MAPK (SAPK) pathways, but the underlying mechanisms remain unclear. Here, we report that the MAP three kinase 1 (MTK1) SAPK kinase kinase (SAPKKK) functions as an oxidative-stress sensor that perceives the cellular redox state and transduces it into SAPK signaling. Following oxidative stress, MTK1 is rapidly oxidized and gradually reduced at evolutionarily conserved cysteine residues. Th
Mammalian cells are frequently exposed to a variety of environmental stresses, such as ultraviolet rays, ionizing radiation, genotoxins, heat shock, and oxidative stress. In coping with the barrage of these and other stresses, multi-cellular eukaryotic organisms have developed a strategy as to how damaged cells will respond to stresses. In general, if the intensity of the damage is moderate, the cell will seek to repair the damage. If, however, the damage to a cell is too severe to be repaired,
Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs selectively on serine and/or threonine residues of cytoplasmic and nuclear proteins, and dynamically regulates their molecular functions. Since conventional strategies to evaluate the O-GlcNAcylation level of a specific protein require time-consuming steps, the development of a rapid and easy method for the detection and quantification of an O-GlcNAcylated protein has been a challenging issue. Here, we describe
We report a case of hypereosinophilic syndrome (HES) with marked eosinophilia (59.7%) and mononeuritis multiplex (upper limbs and buttocks). Necrosis of the finger tips was the primary manifestation which simultaneously occurred on both sides. These clinical manifestations were improved dramatically by subsequent steroid therapy. Interestingly, an elevation of serum tumor necrosis factor (TNF) was observed. These findings suggest that TNF may play a role in the etiology of necrosis of the finger
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