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Docosahexaenoic acid induces the degradation of HPV E6/E7 oncoproteins by activating the ubiquitin-proteasome system.

Abstract：

:The oncogenic human papillomavirus (HPV) E6/E7 proteins are essential for the onset and maintenance of HPV-associated malignancies. Here, we report that activation of the cellular ubiquitin-proteasome system (UPS) by the omega-3 fatty acid, docosahexaenoic acid (DHA), leads to proteasome-mediated degradation of E6/E7 viral proteins and the induction of apoptosis in HPV-infected cancer cells. The increases in UPS activity and degradation of E6/E7 oncoproteins were associated with DHA-induced overproduction of mitochondrial reactive oxygen species (ROS). Exogenous oxidative stress and pharmacological induction of mitochondrial ROS showed effects similar to those of DHA, and inhibition of ROS production abolished UPS activation, E6/E7 viral protein destabilization, and apoptosis. These findings identify a novel role for DHA in the regulation of UPS and viral proteins, and provide evidence for the use of DHA as a mechanistically unique anticancer agent for the chemoprevention and treatment of HPV-associated tumors.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Jing K,Shin S,Jeong S,Kim S,Song KS,Park JH,Heo JY,Seo KS,Park SK,Kweon GR,Wu T,Park JI,Lim K

doi

10.1038/cddis.2014.477

subject

Has Abstract

pub_date

2014-11-13 00:00:00

pages

e1524

issn

2041-4889

pii

cddis2014477

journal_volume

5

pub_type

杂志文章

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