MuLV IN mutants responsive to HDAC inhibitors enhance transcription from unintegrated retroviral DNA.
MuLV IN mutants responsive to HDAC inhibitors enhance transcription from unintegrated retroviral DNA.
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DOI：
10.1016/j.virol.2012.01.034
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发表时间：
2012-05-10
期刊：
影响因子：
3.7
通讯作者：
Roth MJ
中科院分区：
文献类型：
--
作者：
Schneider WM;Wu DT;Amin V;Aiyer S;Roth MJ
对于莫洛尼鼠白血病病毒 (M-MuLV)，持续的病毒感染需要整合原病毒的表达。对于许多应用，非整合逆转录病毒载体已被用来避免整合的不良影响，然而，未整合DNA的表达水平明显低于整合原病毒的表达水平。我们发现，当 HDAC 抑制剂（例如 TSA）与整合酶 (IN) 突变结合使用时，未整合的 DNA 表达会增加。这些突变体包括活性位点突变以及催化活性IN，其在IN的MuLV C端结构域中带有K376突变。 MuLV IN K376 与 HIV-1 IN 中的 K266 同源，HIV-1 IN 是已知的乙酰化底物。 MuLV IN 蛋白在体外被 p300 乙酰化，然而，HDAC 抑制剂对未整合 DNA 基因表达的影响并不依赖于 MuLV IN K376 的乙酰化状态。
For Moloney murine leukemia virus (M-MuLV), sustained viral infections require expression from an integrated provirus. For many applications, non-integrating retroviral vectors have been utilized to avoid the unwanted effects of integration, however, the level of expression from unintegrated DNA is significantly less than that of integrated provirus. We find that unintegrated DNA expression can be increased in the presence of HDAC inhibitors, such as TSA, when applied in combination with integrase (IN) mutations. These mutants include an active site mutation as well as catalytically active INs bearing mutations of K376 in the MuLV C-terminal domain of IN. MuLV IN K376 is homologous to K266 in HIV-1 IN, a known substrate for acetylation. The MuLV IN protein is acetylated by p300 in vitro, however, the effect of HDAC inhibitors on gene expression from unintegrated DNA is not dependent on the acetylation state of MuLV IN K376.
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DOI：
10.1073/pnas.81.20.6461
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DONEHOWER, LA;VARMUS, HE
通讯作者：
VARMUS, HE
影响因子：
4.8
作者：
Cherepanov, P;Maertens, G;Debyser, Z
通讯作者：
Debyser, Z
DOI：
10.1073/pnas.90.13.6125
发表时间：
1993-07-01
影响因子：
11.1
作者：
BUKRINSKY, MI;SHAROVA, N;STEVENSON, M
通讯作者：
STEVENSON, M
DOI：
10.1073/pnas.150220297
发表时间：
2000-07-18
影响因子：
11.1
作者：
Chen, JCH;Krucinski, J;Stroud, RM
通讯作者：
Stroud, RM
影响因子：
6.7
作者：
Bruce, James W.;Ahlquist, Paul;Young, John A. T.
通讯作者：
Young, John A. T.