p53 tumor suppressor protein stability and transcriptional activity are targeted by Kaposi's sarcoma-associated herpesvirus-encoded viral interferon regulatory factor 3.

[primary effusion lymphoma]

Viruses have developed numerous strategies to counteract the host cell defense . Kaposi 's sarcoma -associated herpesvirus (KSHV ) is a DNA tumor virus linked to the development of Kaposi 's sarcoma , Castleman 's disease , and primary effusion lymphoma (PEL ). The virus-encoded viral interferon regulatory factor 3 (vIRF-3 ) gene is a latent gene which is involved in the regulation of apoptosis , cell cycle , antiviral immunity , and tumorigenesis . vIRF-3 was shown to interact with p 53 and inhibit p 53 -mediated apoptosis . However , the molecular mechanism underlying this phenomenon has not been established . Here , we show that vIRF-3 associates with the DNA-binding domain of p 53 , inhibits p 53 phosphorylation on serine residues S 15 and S 20 , and antagonizes p 53 oligomerization and the DNA-binding affinity . Furthermore , vIRF-3 destabilizes p 53 protein by increasing the levels of p 53 polyubiquitination and targeting p 53 for proteasome-mediated degradation . Consequently , vIRF-3 attenuates p 53 -mediated transcription of the growth -regulatory p 21 gene . These effects of vIRF-3 are of biological relevance since the knockdown of vIRF-3 expression in KSHV-positive BC -3 cells , derived from PEL , leads to an increase in p 53 phosphorylation , enhancement of p 53 stability , and activation of p 21 gene transcription . Collectively , these data suggest that KSHV evolved an efficient mechanism to downregulate p 53 function and thus facilitate uncontrolled cell proliferation and tumor growth .

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Diseases presenting "developed numerous strategies to counteract the host cell" symptom

primary effusion lymphoma

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