Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
Facultad de Nutrición, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico.
Mol Cancer Res. 2021 Feb;19(2):167-179. doi: 10.1158/1541-7786.MCR-20-0491. Epub 2020 Oct 26.
The human papillomavirus (HPV) is recognized as the main etiologic agent associated with cervical cancer. HPVs are epitheliotropic, and the ones that infect the mucous membranes are classified into low-risk (LR) and high-risk (HR) types. LR-HPVs produce benign lesions, whereas HR-HPVs produce lesions that may progress to cancer. HR-HPV types 16 and 18 are the most frequently found in cervical cancer worldwide. E6 and E7 are the major HPV oncogenic proteins, and they have been profusely studied. Moreover, it has been shown that the HPV16 E5 (16E5) oncoprotein generates transformation, although the molecular mechanisms through which it carries out its activity have not been well defined. In contrast to and , the open reading frame is lost during the integration of the episomal HPV DNA into the cellular genome. This suggests that E5 acts at the early stages of the transformation process. In this review, we focused on the biochemical characteristics and functions of the HPV E5 oncoprotein, mainly on its association with growth factor receptors and other cellular proteins. Knowledge of the HPV E5 biology is important to understand the role of this oncoprotein in maintaining the viral cycle through the modulation of proliferation, differentiation, and apoptosis, as well as the alteration of other processes, such as survival, adhesion, migration, and invasion during early carcinogenesis. Finally, we summarized recent research that uses the E5 oncoprotein as a therapeutic target, promising a novel approach to the treatment of cervical cancer in its early stages.
人乳头瘤病毒（HPV）被认为是与宫颈癌相关的主要病因。HPV 是上皮嗜性的，感染黏膜的 HPV 分为低危型（LR）和高危型（HR）。LR-HPV 会产生良性病变，而 HR-HPV 则可能导致病变进展为癌症。在全球范围内，HR-HPV 型 16 和 18 是最常见的宫颈癌致病 HPV 型。E6 和 E7 是 HPV 的主要致癌蛋白，已进行了广泛研究。此外，已经表明 HPV16 E5（16E5）致癌蛋白可产生转化，尽管其发挥活性的分子机制尚未明确。与 和 不同，在游离 HPV DNA 整合到细胞基因组时，开放阅读框丢失。这表明 E5 在转化过程的早期阶段发挥作用。在这篇综述中，我们重点关注 HPV E5 致癌蛋白的生化特性和功能，主要关注其与生长因子受体和其他细胞蛋白的关联。了解 HPV E5 的生物学特性对于理解该致癌蛋白在通过调节增殖、分化和凋亡来维持病毒周期，以及在早期癌变过程中改变其他过程（如存活、黏附、迁移和侵袭）方面的作用非常重要。最后，我们总结了最近使用 E5 致癌蛋白作为治疗靶点的研究，为早期宫颈癌的治疗提供了一种新方法。
