Low expression of certain ribosomal proteins leads to the inactivation of p53, which is mediated mainly by RPL5 or RPL11 (ribosomal protein L11). It is also unknown what mechanisms drive aberrant ribosomal proteins expression in tumor. SRBD1 (S1 RNA‐binding domain 1), as a highly conserved RNA‐binding protein, is lowly expressed in glioma tissues and correlated with glioma prognosis. In this study, we observed that SRBD1 was closely related to p53 signaling. The upregulation of SRBD1 elevated p53 levels, thereby activating the p53 signaling pathway. As an RNA bind protein, SRBD1 could bind to the 5′‐UTR of target genes and regulate RNA translation. We further conducted RNA immunoprecipitation using anti‐SRDB1 antibody and noticed 29 hub RNA, including RPL11. RPL11 could inhibit MDM2‐mediated p53 ubiquitination. SRBD1 upregulation promoted RPL11 binding to MDM2 via elevating RPL11 protein levels, which in turn activated the p53 signaling. Disrupting the p53 signaling blocked SRBD1‐induced glioma suppression. In mouse xenograft model, SRBD1 ectopic expression was effective in reducing the total M2 tumor‐associated macrophages (TAMs) density and suppressed glioma tumor growth. In summary, these data show that SRBD1 has a critical role in inhibition of glioma tumor growth and M2 macrophage polarization, and targeting RPL11‐MDM2‐p53 signaling may be an effective strategy to improve therapy and survival for glioma patients.

中文翻译：

---

SRBD1 在神经胶质瘤中通过 RPL11-MDM2-p53 通路调节细胞周期、细胞凋亡和 M2 巨噬细胞极化


某些核糖体蛋白的低表达导致 p53 失活，这主要由 RPL5 或 RPL11（核糖体蛋白 L11）介导。目前尚不清楚哪些机制驱动肿瘤中异常的核糖体蛋白表达。SRBD1 （S1 RNA 结合域 1） 作为一种高度保守的 RNA 结合蛋白，在神经胶质瘤组织中低表达，与神经胶质瘤预后相关。在这项研究中，我们观察到 SRBD1 与 p53 信号传导密切相关。SRBD1 的上调提高了 p53 水平，从而激活了 p53 信号通路。作为一种 RNA 结合蛋白，SRBD1 可以与靶基因的 5′-UTR 结合并调节 RNA 翻译。我们进一步使用抗 SRDB1 抗体进行了 RNA 免疫沉淀，并注意到 29 个枢纽 RNA，包括 RPL11。RPL11 可抑制 MDM2 介导的 p53 泛素化。SRBD1 上调通过提高 RPL11 蛋白水平促进 RPL11 与 MDM2 的结合，进而激活 p53 信号传导。破坏 p53 信号传导阻断了 SRBD1 诱导的神经胶质瘤抑制。在小鼠异种移植模型中，SRBD1 异位表达可有效降低 M2 肿瘤相关巨噬细胞 （TAM） 总密度并抑制神经胶质瘤肿瘤生长。综上所述，这些数据表明 SRBD1 在抑制胶质瘤肿瘤生长和 M2 巨噬细胞极化方面起关键作用，靶向 RPL11-MDM2-p53 信号传导可能是改善胶质瘤患者治疗和生存率的有效策略。