Kyoto University · Biochemistry, Genetics and Molecular Biology
Professor Kazuhiro Iwaï's research lab focuses on the molecular mechanisms underlying cellular signaling, protein degradation, and post-translational modifications, particularly ubiquitination and its role in disease pathogenesis. The lab investigates the regulation of key tumor suppressors like pVHL and iron regulatory protein 2 (IRP2), exploring how oxidative stress and iron homeostasis intersect with ubiquitin ligase systems. A central theme is the identification and functional characterization of E3 ubiquitin ligases, such as the VBC-CUL-2 and LUBAC complexes, in controlling NF-κB signaling, apoptosis, and cancer progression. The lab also examines adhesion molecules and cell surface receptors in tumor-endothelial interactions, contributing to understanding metastasis and inflammation.
Figures are computed from collected data and may differ slightly.
Mutations of von Hippel-Lindau disease (VHL) tumor-suppressor gene product (pVHL) are found in patients with dominant inherited VHL syndrome and in the vast majority of sporadic clear cell renal carcinomas. The function of the pVHL protein has not been clarified. pVHL has been shown to form a complex with elongin B and elongin C (VBC) and with cullin (CUL)-2. In light of the structural analogy of VBC-CUL-2 to SKP1-CUL-1-F-box ubiquitin ligases, the ubiquitin ligase activity of VBC-CUL-2 was exam
The recently identified Fas antigen (Ag) is a cell surface molecule that can mediate apoptosis. The cytoplasmic product of proto-oncogene bcl-2 has been shown to prolong the cellular survival by inhibiting apoptosis. To elucidate the physiologic significance of expression of both molecules, we examined the expression of Fas Ag and bcl-2 on blood leukocyte populations and evaluated their sensitivity to the cytolytic action of anti-Fas antibody. Although Fas Ag was expressed on a fraction of lymph
The ability of iron to catalyze formation of reactive oxygen species significantly contributes to its toxicity in cells and animals. Iron uptake and distribution is regulated tightly in mammalian cells, in part by iron regulatory protein 2 (IRP2), a protein that is degraded efficiently by the proteasome in iron-replete cells. Here, we demonstrate that IRP2 is oxidized and ubiquitinated in cells before degradation. Moreover, iron-dependent oxidation converts IRP2 into a substrate for ubiquitinati
Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alp
Linear ubiquitinylation, a newly identified post-translational modification, is catalyzed by the linear ubiquitin assembly complex (LUBAC), which is composed of three different subunits, HOIL-1L (heme-oxidized IRP2 ligase 1L), HOIP (HOIL-1 interacting protein), and SHARPIN (SHANK-associated RH domain-interacting protein). LUBAC plays a critical role in the activation of nuclear factor-κB (NF-κB) signaling triggered by a variety of stimuli, including tumor necrosis factor-α (TNF-α), interleukin-1
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