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Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways.

Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways.
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Kumari P, Saha I, Narayanan A, Narayanan S, Takaoka A, Kumar NS, Tailor P, Kumar H,


Kumari P, Saha I, Narayanan A, Narayanan S, Takaoka A, Kumar NS, Tailor P, Kumar H, (click to view)

Kumari P, Saha I, Narayanan A, Narayanan S, Takaoka A, Kumar NS, Tailor P, Kumar H,

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Cell death & disease 2017 10 058(10) e3078 doi 10.1038/cddis.2017.461
Abstract

Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown. Here, we identified a conserved herpesviral tegument protein known as pUL48 of HCMV, encoding deubiquitinase enzyme, as having a key role in carcinogenesis. We show using deubiquitinase sufficient- and deficient-HCMV that HCMV deubiquitinase is a key in inducing enhanced cellular metabolic activity through upregulation of several anti-apoptotic genes and downregulation of several pro-apoptotic genes expression. Furthermore, HCMV deubiquitinase acquires pro-tumor functions by inhibiting PRR-mediated type I interferon via deubiquitination of TRAF6, TRAF3, IRAK1, IRF7 and STING. Taken together, our results suggest that HCMV infection may promote oncogenesis by inhibiting innate immunity of the host.

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