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Article Dans Une Revue Nucleic Acids Research Année : 2012

The HTLV-1-encoded protein HBZ directly inhibits the acetyl transferase activity of p300/CBP

Résumé

The homologous cellular coactivators p300 and CBP contain intrinsic lysine acetyl transferase (termed HAT) activity. This activity is responsible for acetyl-ation of several sites on the histones as well as modification of transcription factors. In a previous study, we found that HBZ, encoded by the Human T-cell Leukemia Virus type 1 (HTLV-1), binds to multiple domains of p300/CBP, including the HAT domain. In this study, we found that HBZ inhibits the HAT activity of p300/CBP through the bZIP domain of the viral protein. This effect correlated with a reduction of H3K18 acetylation, a specific target of p300/CBP, in cells expressing HBZ. Interestingly, lower levels of H3K18 acetylation were detected in HTLV-1 infected cells compared to non-infected cells. The inhibitory effect of HBZ was not limited to histones, as HBZ also inhibited acetylation of the NF-iB subunit, p65, and the tumor suppressor, p53. Recent studies reported that mutations in the HAT domain of p300/ CBP that cause a defect in acetylation are found in certain types of leukemia. These observations suggest that inhibition of the HAT activity by HBZ is important for the development of adult T-cell leukemia associated with HTLV-1 infection.

Domaines

Virologie
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hal-02120125 , version 1 (06-07-2020)

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Paternité - Pas d'utilisation commerciale

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Torsten Wurm, Diana G. Wright, Nicholas Polakowski, Jean-Michel Mesnard, Isabelle Lemasson. The HTLV-1-encoded protein HBZ directly inhibits the acetyl transferase activity of p300/CBP. Nucleic Acids Research, 2012, 40 (13), pp.5910-5925. ⟨10.1093/nar/gks244⟩. ⟨hal-02120125⟩
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