- Masayuki Komada
- Toshiaki Fukushima
Regulatory mechanisms of growth factor receptor downregulation
The levels of plasma membrane proteins are strictly regulated depending on the cellular situations, impairment of which results in a variety of disease conditions. For instance, overexpression of growth factor receptors leads to tumorigenesis. To control the levels of plasma membrane proteins, cells incorporate plasma membrane proteins which should be downregulated by endocytosis, and transport them to the lysosome for degradation. Here, ubiquitination of plasma membrane proteins serves as a tag which selectively directs them to the lysosome.
In Komada Lab, we study the regulatory mechanisms of lysosomal trafficking of plasma membrane proteins (growth factor receptors in particular). In addition, by examining the relevance of their impairment to tumorigenesis, we try to return the results of basic cell biology to medicine and society. Currently, we focus on mutations in the deubiquitinase USP8 which causative of pituitary tumors leading to the intractable disease “Cushing’s disease”.
- 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.
- Tanno H, Yamaguchi T, Goto E, Ishido S, Komada M. The Ankrd 13 family of UIM- bearing proteins regulates EGF receptor endocytosis from the plasma membrane. Mol. Biol. Cell 2012, 23, 1343-1353.
- Mukai A, Yamamoto-Hino M, Awano W, Watanabe W, Komada M, Goto S. Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J. 2010, 29, 2114-2125.