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首页> 外文期刊>Cell death and differentiation >E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis.
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E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis.

机译：E3泛素连接酶TRIM32负调节肿瘤抑制因子p53，促进肿瘤发生。

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摘要

Tumor suppressor p53 has a key role in maintaining genomic stability and preventing tumorigenesis through its regulation of cellular stress responses, including apoptosis, cell cycle arrest and senescence. To ensure its proper levels and functions in cells, p53 is tightly regulated mainly through post-translational modifications, such as ubiquitination. Here, we identified E3 ubiquitin ligase TRIM32 as a novel p53 target gene and negative regulator to regulate p53-mediated stress responses. In response to stress, such as DNA damage, p53 binds to the p53 responsive element in the promoter of the TRIM32 gene and transcriptionally induces the expression of TRIM32 in cells. In turn, TRIM32 interacts with p53 and promotes p53 degradation through ubiquitination. Thus, TRIM32 negatively regulates p53-mediated apoptosis, cell cycle arrest and senescence in response to stress. TRIM32 is frequently overexpressed in different types of human tumors. TRIM32 overexpression promotes cell oncogenic transformation and tumorigenesis in mice in a largely p53-dependent manner. Taken together, our results demonstrated that as a novel p53 target and a novel negative regulator for p53, TRIM32 has an important role in regulation of p53 and p53-mediated cellular stress responses. Furthermore, our results also revealed that impairing p53 function is a novel mechanism for TRIM32 in tumorigenesis.
机译：肿瘤抑制因子p53通过调节细胞应激反应（包括凋亡，细胞周期停滞和衰老），在维持基因组稳定性和预防肿瘤发生中起关键作用。为了确保其在细胞中的适当水平和功能，p53主要通过翻译后修饰（例如泛素化）来严格调节。在这里，我们确定E3泛素连接酶TRIM32为新型p53靶基因和负调节剂，以调节p53介导的应激反应。在对压力（例如DNA损伤）的反应中，p53与TRIM32基因启动子中的p53响应元件结合，并转录诱导TRIM32在细胞中的表达。反过来，TRIM32与p53相互作用并通过泛素化促进p53降解。因此，TRIM32对应激反应负调控p53介导的细胞凋亡，细胞周期停滞和衰老。 TRIM32在不同类型的人类肿瘤中经常过表达。 TRIM32过表达在很大程度上以p53依赖性的方式促进了小鼠的细胞致癌转化和肿瘤发生。两者合计，我们的结果表明，作为p53的新型p53靶标和新型负调节剂，TRIM32在调节p53和p53介导的细胞应激反应中具有重要作用。此外，我们的结果还表明，削弱p53功能是TRIM32在肿瘤发生中的新机制。

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