GRWD1, a new player among oncogenesis-related ribosomal/nucleolar proteins

ABSTRACT

Increasing attention has been paid to certain ribosomal 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. 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 clarified whether many of these factors can actually prevent tumorigenesis and if so, how they do so. Conversely, some ribosomal/nucleolar proteins promote tumorigenesis. For example, PICT1 binds to and anchors RPL11 in nucleoli, down-regulating p53 and promoting tumorigenesis. GRWD1 was recently identified as another such factor. When overexpressed, GRWD1 suppresses p53 and transforms normal human cells, probably by binding to RPL11 and sequestrating it from MDM2. However, other pathways may also be involved.

KEYWORDS:

• GRWD1
• nucleolar stress response
• oncogene
• p53
• PICT1
• RPL11
• tumor suppressor

Disclosure of potential conflicts of interest

The authors declare no conflicts of interest in relation to this article.

Acknowledgment

We thank all members of our research group for helpful discussions and critical reading of the manuscript.

Funding

This work was supported in part by grants to Nozomi Sugimoto and Masatoshi Fujita from the Ministry of Education, Science, Sports, Technology and Culture of Japan.