Guanylate-binding protein 1 (GBP1) is a large GTPase of the dynamin superfamily involved in the regulation of membrane, cytoskeleton, and cell cycle progression dynamics. In many cell types, such as endothelial cells and monocytes, GBP1 expression is strongly provoked by interferon γ (IFNγ) and acts to restrain cellular proliferation in inflammatory contexts. In immunity, GBP1 activity is crucial for the maturation of autophagosomes infected by intracellular pathogens and the cellular response to pathogen-associated molecular patterns. In chronic inflammation, GBP1 activity inhibits endothelial cell proliferation even as it protects from IFNγ-induced apoptosis. A similar inhibition of proliferation has also been found in some tumor models, such as colorectal or prostate carcinoma mouse models. However, this activity appears to be context-dependent, as in other cancers, such as oral squamous cell carcinoma and ovarian cancer, GBP1 activity appears to anchor a complex, taxane chemotherapy resistance profile where its expression levels correlate with worsened prognosis in patients. This discrepancy in GBP1 function may be resolved by GBP1's involvement in the induction of a cellular senescence phenotype, wherein anti-proliferative signals coincide with potent resistance to apoptosis and set the stage for dysregulated proliferative mechanisms present in growing cancers to hijack GBP1 as a pro- chemotherapy treatment resistance (TXR) and pro-survival factor even in the face of continued cytotoxic treatment. While the structure of GBP1 has been extensively characterized, its roles in inflammation, TXR, senescence, and other biological functions remain under-investigated, although initial findings suggest that GBP1 is a compelling target for therapeutic intervention in a variety of conditions ranging from chronic inflammatory disorders to cancer.

中文翻译：

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鸟苷酸结合蛋白1：炎症和癌症中的新兴目标。

鸟苷酸结合蛋白1（GBP1）是动态超家族的大GTPase，参与膜，细胞骨架和细胞周期进程动态的调控。在许多细胞类型中，例如内皮细胞和单核细胞，GBP1的表达被干扰素γ（IFNγ）强烈激发，并在炎性环境中起到抑制细胞增殖的作用。在免疫方面，GBP1活性对于细胞内病原体感染的自噬体的成熟以及细胞对病原体相关分子模式的反应至关重要。在慢性炎症中，GBP1活性可抑制内皮细胞增殖，即使它可防止IFNγ诱导的细胞凋亡。在某些肿瘤模型，例如结直肠或前列腺癌小鼠模型中，也发现了类似的增殖抑制作用。但是，此活动似乎与上下文有关，与其他癌症（例如口腔鳞状细胞癌和卵巢癌）一样，GBP1活性似乎锚定了一个复杂的紫杉烷化疗耐药性，其表达水平与患者预后恶化相关。GBP1功能的这种差异可以通过GBP1参与诱导细胞衰老表型来解决，其中抗增殖信号与对细胞凋亡的强抗性相吻合，并为生长中的癌症存在增殖失调的机制奠定了基础，从而劫持了GBP1作为亲即使面对持续的细胞毒性治疗，化疗药物的耐药性（TXR）和促生存因子也是如此。尽管GBP1的结构已得到广泛表征，但其在炎症，TXR，衰老和其他生物学功能中的作用仍未得到充分研究，