HCMV IE2-mediated inhibition of HAT activity downregulates p53 function
Resource
The EMBO Journal 23, 2269–2280
Journal
The EMBO Journal 23, 2269–2280
Pages
-
Date Issued
2004
Date
2004
Author(s)
Wang, Y.H.
Lee, S.C.
Hsu, C.H.
Chang, Margaret DT
Tai, K.Y.
Yang, Y.T.
Wang, P.S.
Chen, C.J.
Wu, C.We.
Juan, L.J.
DOI
246246/2006111501221915
Abstract
Targeting of cellular histone acetyltransferases (HATs) by
viral proteins is important in the development of virusassociated
diseases. The immediate-early 2 protein (IE2) of
human cytomegalovirus (HCMV) binds to the tumor suppressor,
p53, and inactivates its functions by unknown
mechanisms. Here, we show that IE2 binds to the HAT
domain of the p53 coactivators, p300 and CREB-binding
protein (CBP), and blocks their acetyltransferase activity
on both histones and p53. The minimal HAT inactivation
region on IE2 involves the N-terminal 98 amino acids. The
in vivo DNA binding of p53 and local histone acetylation
on p53-dependent promoters are all reduced by IE2, but
not by mutant IE2 proteins that lack the HAT inhibition
region. Furthermore, the p53 acetylation site mutant,
K320/373/382R, retains both DNA binding and promoter
transactivation activity in vivo and these effects are repressed
by IE2 as well. Together with the finding that only
wild-type IE2 exerts an antiapoptotic effect, our results
suggest that HCMV IE2 downregulates p53-dependent
gene activation by inhibiting p300/CBP-mediated local
histone acetylation and that IE2 may have oncogenic
activity.
Subjects
IE2
HAT
HCMV
p53
SDGs
Publisher
Taipei:National Taiwan University Department of Molecular Medicine
Type
journal article
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