The skin represents a physical and chemical barrier against invading pathogens, which is additionally supported by restriction factors that provide intrinsic cellular immunity. These factors detect viruses to block their replication cycle. Here, we uncover the Myb-related transcription factor, partner of profilin (MYPOP) as a novel antiviral protein. It is highly expressed in the epithelium and binds to the minor capsid protein L2 and the DNA of human papillomaviruses (HPV), which are the primary causative agents of cervical cancer and other tumors. The early promoter activity and early gene expression of the oncogenic HPV types 16 and 18 is potently silenced by MYPOP. Cellular MYPOP-depletion relieves the restriction of HPV16 infection, demonstrating that MYPOP acts as a restriction factor. Interestingly, we found that MYPOP protein levels are significantly reduced in diverse HPV-transformed cell lines and in HPV-induced cervical cancer. Decades ago it became clear that the early oncoproteins E6 and E7 cooperate to immortalize keratinocytes by promoting degradation of tumor suppressor proteins. Our findings suggest that E7 stimulates MYPOP degradation. Moreover, overexpression of MYPOP blocks colony formation of HPV and non-virally transformed keratinocytes, suggesting that MYPOP exhibits tumor suppressor properties.

中文翻译：

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Myb相关蛋白MYPOP是致癌性人乳头瘤病毒的新型内在宿主限制性因子。

皮肤代表了抵御病原体入侵的物理和化学屏障，此外还受到提供固有细胞免疫力的限制因子的支持。这些因素检测到病毒以阻止其复制周期。在这里，我们发现Myb相关转录因子，profilin（MYPOP）的伴侣，是一种新型抗病毒蛋白。它在上皮细胞中高度表达，并与次要衣壳蛋白L2和人乳头瘤病毒（HPV）的DNA结合，后者是子宫颈癌和其他肿瘤的主要病因。MYPOP强力沉默了16型和18型致癌HPV的早期启动子活性和早期基因表达。细胞MYPOP耗竭减轻了对HPV16感染的限制，表明MYPOP充当了限制因子。有趣的是，我们发现，在各种HPV转化的细胞系和HPV诱导的宫颈癌中，MYPOP蛋白水平显着降低。几十年前，很明显，早期癌蛋白E6和E7通过促进肿瘤抑制蛋白的降解而协同作用，从而使角质形成细胞永生。我们的发现表明E7刺激MYPOP降解。此外，MYPOP的过表达会阻止HPV和非病毒转化的角质形成细胞的集落形成，这表明MYPOP具有抑癌作用。