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@ARTICLE{Boehm:274207,
author = {D. Boehm and V. Lam and M. Schnölzer$^*$ and M. Ott},
title = {{T}he lysine methyltransferase {SMYD}5 amplifies {HIV}-1
transcription and is post-transcriptionally upregulated by
{T}at and {USP}11.},
journal = {Cell reports},
volume = {42},
number = {3},
issn = {2211-1247},
address = {[New York, NY]},
publisher = {Elsevier},
reportid = {DKFZ-2023-00493},
pages = {112234},
year = {2023},
abstract = {A successful HIV-1 cure strategy may require enhancing
HIV-1 latency to silence HIV-1 transcription. Modulators of
gene expression show promise as latency-promoting agents in
vitro and in vivo. Here, we identify Su(var)3-9,
enhancer-of-zeste, and trithorax (SET) and myeloid, Nervy,
and DEAF-1 (MYND) domain-containing protein 5 (SMYD5) as a
host factor required for HIV-1 transcription. SMYD5 is
expressed in CD4+ T cells and activates the HIV-1 promoter
with or without the viral Tat protein, while knockdown of
SMYD5 decreases HIV-1 transcription in cell lines and
primary T cells. SMYD5 associates in vivo with the HIV-1
promoter and binds the HIV trans-activation response (TAR)
element RNA and Tat. Tat is methylated by SMYD5 in vitro,
and in cells expressing Tat, SMYD5 protein levels are
increased. The latter requires expression of the Tat
cofactor and ubiquitin-specific peptidase 11 (USP11). We
propose that SMYD5 is a host activator of HIV-1
transcription stabilized by Tat and USP11 and, together with
USP11, a possible target for latency-promoting therapy.},
keywords = {CP: Microbiology (Other) / HIV-1 (Other) / SMYD5 (Other) /
TAR RNA (Other) / Tat (Other) / USP11 (Other) / latency
(Other)},
cin = {B100},
ddc = {610},
cid = {I:(DE-He78)B100-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36897778},
doi = {10.1016/j.celrep.2023.112234},
url = {https://inrepo02.dkfz.de/record/274207},
}