GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system

• DOI: 10.1242/jcs.213009
• Publication Date: 2018-07-10T14:25:14Z
• Authors: Shinya Watanabe; Hiroki Fujiyama; Takuya Takafuji; Kota Kayama; Masaki Matsumoto; Keiichi I. Nakayama; Kazumasa Yoshida; Nozomi Sugimoto; Masatoshi Fujita
• Keywords: Ribosomal protein

ABSTRACT Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a Cdt1-binding protein that promotes mini-chromosome maintenance (MCM) loading through its histone chaperone activity. GRWD1 acts as tumor-promoting factor by downregulating p53 (also known TP53) via the RPL11–MDM2–p53 axis. Here, we identified GRWD1-interacting proteins using proteomics approach and showed interacts with various involved in transcription, translation, DNA replication repair, chromatin organization, ubiquitin-mediated proteolysis. We focused on ribosomal L23 (RPL23), which positively regulates nucleolar stress responses MDM2 binding inhibition, thereby functioning tumor suppressor. Overexpression of decreased RPL23 levels stability; this effect was restored upon treatment proteasome inhibitor MG132. EDD UBR5), an E3 ubiquitin ligase GRWD1, also downregulated RPL23, decrease further enhanced co-expression GRWD1. Conversely, siRNA-mediated knockdown upregulated RPL23. Co-expression promoted ubiquitylation. These data suggest together to negatively regulate ubiquitin-proteasome system. expression reversed RPL23-mediated inhibition anchorage-independent growth cancer cells. Our GRWD1-induced proteolysis plays role downregulation tumorigenesis.