Inactivation of CREB mediated gene transcription by HDAC8 bound protein phosphatase.
Inactivation of CREB mediated gene transcription by HDAC8 bound protein phosphatase.
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DOI：
10.1016/j.bbrc.2008.11.135
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发表时间：
2009-01-30
影响因子：
3.1
通讯作者：
Xia, Houhui
中科院分区：
文献类型：
--
作者：
Gao, Jingxia;Siddoway, Benjamin;Huang, Qing;Xia, Houhui
通过丝氨酸133处的磷酸化激活CREB并产生CREB介导的基因表达是关键事件，其可对许多细胞过程（包括细胞存活和可塑性）具有显著影响。CREB可以被许多激酶激活，例如，它可以被PKA、MAPK和CaMKIV磷酸化。导致CREB激活的各种信号通路已被广泛研究。另一方面，CREB被PP1通过S133处的去磷酸化而失活，并且没有太多关注信号通路的这一方面。最近研究表明，PP 1可以通过PP 1结合蛋白HDAC 1靶向CREB，实现有效的去磷酸化。在这项研究中，我们发现另一种I类HDAC家族蛋白HDAC 8定位于HEK 293细胞的细胞核中，并且也与CREB和PP 1结合。重组HDAC 8的表达导致响应于毛喉素应用的CREB活化和CREB介导的基因转录降低。因此，我们的研究阐明，一个以上的I类HDAC家族成员可以调节CREB介导的基因转录的持续时间。
CREB activation via phosphorylation at serine 133 and resulting CREB mediated gene expression is a critical event which can have a significant effect on many cellular processes, including cell survival and plasticity. CREB can be activated by many kinases, for example, it can be phosphorylated by PKA, MAPK, and CaMKIV. The various signaling pathways leading to CREB activation have been extensively studied. On the other hand, CREB is inactivated by PP1 through dephosphorylation at S133 and not much attention has been paid to this aspect of the signaling pathway. It was shown recently that PP1 can be targeted to CREB, for efficient dephosphorylation, through PP1 binding protein HDAC1. In this study, we found that another class-I HDAC family protein, HDAC8, localized in the nucleus of HEK293 cells and also bound to both CREB and PP1. Expression of recombinant HDAC8 results in decreased CREB activation and CREB mediated gene transcription in response to forskolin application. Our study thus elucidated that more than one class-I HDAC family members can regulate the duration of CREB mediated gene transcription.
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DOI：
10.1073/pnas.191352298
发表时间：
2001-09-25
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
16.2
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通讯作者：
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影响因子：
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影响因子：
4.7
作者：
Hu, Xiao Dong;Huang, Qing;Xia, Houhui
通讯作者：
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DOI：
10.1073/pnas.211563998
发表时间：
2001-12-18
影响因子：
11.1
作者：
Mermelstein, PG;Deisseroth, K;Tsien, RW
通讯作者：
Tsien, RW