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核糖体蛋白L11对HDM2活性的调控

Regulation of HDM2 activity by the ribosomal protein L11.

作者信息

Lohrum Marion A E, Ludwig Robert L, Kubbutat Michael H G, Hanlon Mary, Vousden Karen H

机构信息

Regulation of Cell Growth Laboratory, NCI-FRCDC, Frederick, MD 21702, USA.

出版信息

Cancer Cell. 2003 Jun;3(6):577-87. doi: 10.1016/s1535-6108(03)00134-x.

Abstract

The HDM2 protein plays an important role in regulating the stability and function of the p53 tumor suppressor protein. In this report, we show that the ribosomal protein L11 can interact with HDM2 and inhibit HDM2 function, thus leading to the stabilization and activation of p53. The inhibition of HDM2 activity by L11 shows some similarity to the previously described activity of ARF, and expression of either ARF or L11 can induce a p53 response. Enhancement of the interaction between endogenous L11 and HDM2 following treatment of cells with low levels of actinomycin-D suggests that the HDM2/L11 interaction represents a novel pathway for p53 stabilization in response to perturbations in ribosome biogenesis.

摘要

HDM2蛋白在调节p53肿瘤抑制蛋白的稳定性和功能方面发挥着重要作用。在本报告中,我们表明核糖体蛋白L11可与HDM2相互作用并抑制HDM2功能,从而导致p53的稳定和激活。L11对HDM2活性的抑制与先前描述的ARF活性有一些相似之处,并且ARF或L11的表达均可诱导p53反应。用低水平放线菌素-D处理细胞后,内源性L11与HDM2之间相互作用的增强表明,HDM2/L11相互作用代表了一种在核糖体生物发生受到干扰时p53稳定化的新途径。

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