Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1

Abstract : Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses p53 activity. In HCT116 p53+/+ cells treated with the DNA-damaging agent, etoposide, HBZ reduced p53-mediated activation of p21/CDKN1A and GADD45A expression, which was associated with a delay in G2 phase-arrest. These effects were attributed to direct inhibition of the histone acetyltransferase (HAT) activity of p300/CBP by HBZ, causing a reduction in p53 acetylation, which has be linked to decreased p53 activity. In addition, HBZ bound to, and inhibited the HAT activity of HBO1. Although HBO1 did not acetylate p53, it acted as a coactivator for p53 at the p21/CDKN1A promoter. Therefore, through interactions with two separate HAT proteins, HBZ impairs the ability of p53 to activate transcription. This mechanism may explain how p53 activity is restricted in ATL cells that do not express Tax due to modifications of the HTLV-1 provirus, which accounts for a majority of patient samples.
Complete list of metadatas

Cited literature [106 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02187843
Contributor : Benoit Miotto <>
Submitted on : Thursday, July 18, 2019 - 10:31:59 AM
Last modification on : Wednesday, August 21, 2019 - 10:54:05 AM

File

6424-96636-5-PB.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Diana Wright, Claire Marchal, Kimson Hoang, John Ankney, Stephanie Nguyen, et al.. Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1. Oncotarget, Impact journals, 2016, 7 (2), pp.1687-706. ⟨10.18632/oncotarget.6424⟩. ⟨inserm-02187843⟩

Share

Metrics

Record views

32

Files downloads

41