Cutting edge Seminar
※ Zoom online/ Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle
Speaker: Masatoshi Fujita (Professor, Department of Cellular Biochemistry, Faculty of Pharmaceutical Science, Kyushu University.)
Title：Ribosomal/nucleolar proteins that act as oncogenes or antioncogenes
Date&Time: 11 Nov. (Wed.) 2020, 12:00- 13:00
Venue: Zoom online/ Please check the URL on “HIGO Cutting-Edge Seminar” at Moodle
Summary:
We have been studying the molecular mechanism for regulation of pre-replication complex (pre-RC) formation (Reviewed in Ref.1; 2), during which we identified GRWD1, a nucleolar protein, as a histone chaperone that promotes pre-RC formation (3). Later, it has turned out that GRWD1 is a novel oncogene (4, 5, 6). Thereafter, we have been interested in and studying certain ribosomal/nucleolar or ribosome biosynthesis-related proteins involved in oncogenesis. Members of one group are classified as “tumor suppressive factors” represented by RPL5 and RPL11; loss of their functions leads to cancer predisposition (Reviewed in Ref. 7). RPL5 and RPL11 prevent tumorigenesis by binding to and inhibiting the MDM2 ubiquitin ligase and thereby up-regulating p53. Many other candidate tumor suppressive ribosomal/nucleolar proteins have been suggested. However, it remains to be experimentally proven whether many of these factors can actually prevent tumorigenesis and if so, how they do so. In this regard, we have recently found that RPS7, RPS17, and RPS19 (all of which are causative agents of cancer-prone Diamond-Blackfan anemia) act as tumor suppressors and now try to clarify the molecular mechanisms. Conversely, some ribosomal/nucleolar proteins promote tumorigenesis. For example, we demonstrated that GRWD1 binds to RPL11 and sequestrates it from MDM2, thereby down-regulating p53 and transforming normal human cells (4). In addition, GRWD1, together with EDD ubiquitin ligase, may also down-regulate RPL23, another candidate tumor suppressor, via the ubiquitin-proteasome system (5). I will discuss these ribosomal/nucleolar proteins involved in oncogenesis in detail in HIGO seminar.
References
- Sugimoto and Fujita. Adv. Exp. Med. Biol. 1042, 61-78, (2017).
- Sugimoto et al. Nucleic Acids Res. 46, 6683-6696, (2018).
- Sugimoto et al. Nucleic Acids Res. 43, 5898-5911, (2015).
- Kayama et al. EMBO Rep. 18, 123-137, (2017).
- Watanabe et al. J. Cell Sci. 131, jcs213009, (2018).
- Fujiyama et al. J. Biochem. 167, 15-24, (2020).
- Takafuji et al. Cell Cycle, 16, 1397-1403, (2017).
