Zheng Gang, Yang Yu-Chung
Department of Pharmacology and Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Biochem Biophys Res Commun. 2006 Jan 27;339(4):1069-75. doi: 10.1016/j.bbrc.2005.11.122. Epub 2005 Dec 6.
We previously showed that ZNF76 is a general transcription repressor targeting TATA-binding protein (TBP), through a process regulated by sumoylation [G. Zheng, Y.C. Yang, ZNF76, a novel transcriptional repressor targeting TATA-binding protein, is modulated by sumoylation, J. Biol. Chem. 279 (2004) 42410-42421]. In this study, two additional regulatory mechanisms for ZNF76 were identified. ZNF76 is acetylated by p300 and deacetylated by HDAC1, and acetylation of ZNF76 leads to its loss of sumoylation and attenuation of TBP interaction. Consistent with their physical antagonism, acetylation, and sumoylation play opposite roles in regulating the transactivation of ZNF76. Besides acetylation and sumoylation, ZNF76 is also regulated through mRNA splicing: two isoforms of ZNF76 have different abilities of interacting with TBP. Our study shows that ZNF76, a TBP-interacting transcriptional modulator, is regulated by both lysine modifications and alternative splicing.
我们之前表明，ZNF76是一种靶向TATA结合蛋白（TBP）的一般转录抑制因子，其作用过程受SUMO化调控[G. Zheng，Y.C. Yang，ZNF76，一种靶向TATA结合蛋白的新型转录抑制因子，受SUMO化调控，《生物化学杂志》279 (2004) 42410 - 42421]。在本研究中，我们鉴定出了ZNF76的另外两种调控机制。ZNF76被p300乙酰化并被HDAC1去乙酰化，ZNF76的乙酰化导致其SUMO化丧失以及与TBP相互作用减弱。与它们的物理拮抗作用一致，乙酰化和SUMO化在调节ZNF76的反式激活中发挥相反作用。除了乙酰化和SUMO化，ZNF76还通过mRNA剪接进行调控：ZNF76的两种异构体与TBP相互作用的能力不同。我们的研究表明，ZNF76作为一种与TBP相互作用的转录调节因子，受赖氨酸修饰和可变剪接的双重调控。
