Gao Jingxia, Siddoway Benjamin, Huang Qing, Xia Houhui
Neuroscience Center, LSU Health Science Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA.
Biochem Biophys Res Commun. 2009 Jan 30;379(1):1-5. doi: 10.1016/j.bbrc.2008.11.135. Epub 2008 Dec 12.
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.
通过丝氨酸133位点磷酸化激活CREB以及由此产生的CREB介导的基因表达是一个关键事件，它可对包括细胞存活和可塑性在内的许多细胞过程产生重大影响。CREB可被多种激酶激活，例如，它可被PKA、MAPK和CaMKIV磷酸化。导致CREB激活的各种信号通路已得到广泛研究。另一方面，PP1通过使S133位点去磷酸化使CREB失活，而该信号通路的这一方面并未受到太多关注。最近研究表明，PP1可通过PP1结合蛋白HDAC1靶向作用于CREB，以实现高效去磷酸化。在本研究中，我们发现另一类I型HDAC家族蛋白HDAC8定位于HEK293细胞的细胞核中，并且还与CREB和PP1都结合。重组HDAC8的表达导致在应用福司可林后CREB激活及CREB介导的基因转录减少。因此，我们的研究阐明了不止一种I型HDAC家族成员可调节CREB介导的基因转录的持续时间。
