The Shwachman-Bodian Diamond syndrome (SBDS)-associated gene, SBDS, is involved in rRNA synthesis and ribosome maturation, but the role of SBDS in cancer is largely elusive. In this study, we found that SBDS is often overexpressed or amplified in human cancers, and high level of endogenous SBDS is significantly associated with unfavorable prognosis. Conversely, knockdown of SBDS leads to p53 stabilization and activation through the ribosomal stress-RPL5/RPL11-MDM2 pathway, resulting in the repression of cancer cell proliferation and invasion. Interestingly, ectopic SBDS in the nucleoplasm also suppresses tumor cell growth and proliferation in vitro and in vivo. Mechanistically, ectopically expressed SBDS triggered by, for example, ribosomal stress binds to the transactivation domain of p53 and perturbs the MDM2–p53 interaction, consequently leading to impaired p53 ubiquitination and proteasomal degradation. Altogether, our finding for the first time demonstrates the dual functions of SBDS in cancer development by coordinating ribosome biogenesis and p53 activity.

Shwachman-Bodian Diamond综合征（SBDS）相关基因，SBDS，参与rRNA合成和核糖体成熟，但SBDS在癌症中的作用在很大程度上难以捉摸。在这项研究中，我们发现SBDS在人类癌症中经常过表达或扩增，而高水平的内源性SBDS与不良预后显着相关。相反，敲低SBDS可通过核糖体应激-RPL5 / RPL11-MDM2途径导致p53稳定和激活，从而抑制了癌细胞的增殖和侵袭。有趣的是，核质中的异位SBDS在体外和体内也抑制肿瘤细胞的生长和增殖。从机制上讲，异位表达的SBDS由核糖体应激触发，与p53的反式激活域结合，扰乱了MDM2-p53的相互作用，因此导致p53泛素化和蛋白酶体降解受损。