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The Myb-related protein MYPOP is a novel intrinsic host restriction factor of oncogenic human papillomaviruses.

Abstract：

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Wüstenhagen E,Boukhallouk F,Negwer I,Rajalingam K,Stubenrauch F,Florin L

doi

10.1038/s41388-018-0398-6

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

6275-6284

issue

48

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-018-0398-6

journal_volume

37

pub_type

杂志文章

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