Shih H-M, Chang C-C, Kuo H-Y, Lin D-Y
Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia RD, Taipei 11529, Taiwan.
Biochem Soc Trans. 2007 Dec;35(Pt 6):1397-400. doi: 10.1042/BST0351397.
SUMO (small ubiquitin-related modifier) modification is emerging as an important post-translational control in transcription. In general, SUMO modification is associated with transcriptional repression. Although many SUMO-modified transcription factors and co-activators have been identified, little is known about the mechanism underlying SUMOylation-elicited transcriptional repression. Here, we summarize that SUMO modification of transcription factors such as androgen receptor, glucocorticoid receptor, Smad4 and CBP [CREB (cAMP-response-element-binding protein)-binding protein] co-activator results in the recruitment of a transcriptional co-repressor Daxx, thereby causing transcriptional repression. Such a SUMO-dependent recruitment of Daxx is mediated by the interaction between the SUMO moiety of SUMOylated factors and Daxx SUMO-interacting motif. Interestingly, the transrepression effect of Daxx on these SUMOylated transcription factors can be relieved by SUMOylated PML (promyelocytic leukaemia) via altering Daxx partition from the targeted gene promoter to PML nuclear bodies. Because Daxx SUMO-interacting motif is a common binding site for SUMOylated factors, a model of competition for Daxx recruitment between SUMOylated PML and SUMOylated transcription factors was proposed. Together, our findings strongly suggest that Daxx functions as a SUMO reader in the SUMO-dependent regulation of transcription and subnuclear compartmentalization.
SUMO(小泛素相关修饰物)修饰正成为转录过程中一种重要的翻译后调控方式。一般来说,SUMO修饰与转录抑制相关。尽管已经鉴定出许多SUMO修饰的转录因子和共激活因子,但对于SUMO化引发转录抑制的潜在机制却知之甚少。在此,我们总结发现,雄激素受体、糖皮质激素受体、Smad4和CBP[CREB(环磷酸腺苷反应元件结合蛋白)结合蛋白]共激活因子等转录因子的SUMO修饰会导致转录共抑制因子Daxx的募集,从而引起转录抑制。Daxx这种依赖SUMO的募集是由SUMO化因子的SUMO部分与Daxx的SUMO相互作用基序之间的相互作用介导的。有趣的是,SUMO化的PML(早幼粒细胞白血病)可通过改变Daxx从靶向基因启动子到PML核体的分布,从而解除Daxx对这些SUMO化转录因子的反式抑制作用。由于Daxx的SUMO相互作用基序是SUMO化因子的共同结合位点,因此提出了SUMO化的PML与SUMO化的转录因子之间竞争募集Daxx的模型。总之,我们的研究结果强烈表明,在转录和亚核区室化的SUMO依赖性调控中,Daxx作为一个SUMO阅读器发挥作用。