Komada-Fukushima Lab

Staff

Masayuki Komada
(Professor)
Toshiaki Fukushima
(Associate Professor)

Ubiquitin-dependent integrity of human cells and its abnormalities in disease

Protein ubiquitination is widely recognized as a signal for degradation. However, it also plays diverse roles in regulating the fate of target proteins, such as altering their subcellular localization or promoting protein complex formation. It is estimated that over 50% of human proteins undergo ubiquitination, which is tightly regulated by various factors including ubiquitin ligases and deubiquitinating enzymes. This extensive "ubiquitin system" underpins numerous cellular processes, including protein and organelle quality control, signal transduction, membrane trafficking, DNA repair, cell cycle regulation, cell death, and senescence.

We aim to elucidate the molecular mechanisms by which the ubiquitin system regulates human cellular functions. Our research focuses on growth factor signaling, cell division, the dynamics of organelles such as endosomes and stress granules, and cellular senescence. Furthermore, we investigate how the ubiquitin system is altered in diseases such as cancer and neurodegenerative disorders, as well as in aging. We also conduct translational research to apply our findings to therapeutic strategies and health promotion.

Regulatory mechanisms of growth factor receptor downregulation

Schematic illustration of our discovery that mutations in a deubiquitinating enzyme gene cause Cushing's disease.

Selected publications

Kakihara K, Asamizu K, Moritsugu K, Kubo M, Kitaguchi T, Endo A, Kidera K, Ikeguchi M, Kato A, Komada M, Fukushima T. Molecular basis of ubiquitin-specific protease 8 autoinhibition by the WW-like domain. Commun. Biol. 2021, 4, 1272
Xie X, Matsumoto S, Endo A, Fukushima T, Kawahara H, Saeki Y, Komada M. Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities. J. Cell. Sci. 2018, 131, jcs210856.
Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F, Meitinger T, Mizuno-Yamasaki E, Kawaguchi K, Saeki Y, Tanaka K, Wieland T, Graf E, Saeger W, Ronchi CL, Allolio B, Buchfelder M, Strom TM, Fassnacht M, Komada M. Mutations in the deubiquitinase gene USP8 cause Cushing's disease. Nat. Genet. 2015, 47, 31-38.

Komada-Fukushima Lab Website

Access / S2 building, 5F East (Suzukakedai Campus)