Best Jennifer L, Ganiatsas Soula, Agarwal Sadhana, Changou Austin, Salomoni Paolo, Shirihai Orian, Meluh Pamela B, Pandolfi Pier Paolo, Zon Leonard I
Division of Hematology/Oncology, Children's Hospital, Department of Medicine, Boston, MA 02115, USA.
Mol Cell. 2002 Oct;10(4):843-55. doi: 10.1016/s1097-2765(02)00699-8.
During a screen to identify c-Jun activators, we isolated a cysteine protease, SuPr-1, that induced c-Jun-dependent transcription independently of c-Jun phosphorylation. SuPr-1 is a member of a new family of proteases that hydrolyze the ubiquitin-like modifier, SUMO-1. SuPr-1 hydrolyzed SUMO-1-modified forms of the promyelocytic leukemia gene product, PML, and altered the subcellular distribution of PML in nuclear PODs (PML oncogenic domains). SuPr-1 also altered the distribution of other nuclear POD-associated proteins, such as CBP and Daxx, that act as transcriptional regulators. SuPr-1 action on transcription was enhanced by PML, and SuPr-1 failed to activate transcription in PML-deficient fibroblasts. Our studies establish an important role for SUMO proteases in transcription.
在一次旨在鉴定c-Jun激活因子的筛选过程中，我们分离出一种半胱氨酸蛋白酶SuPr-1，它可独立于c-Jun磷酸化诱导c-Jun依赖性转录。SuPr-1是一个新的蛋白酶家族成员，该家族可水解泛素样修饰物SUMO-1。SuPr-1水解早幼粒细胞白血病基因产物PML的SUMO-1修饰形式，并改变PML在核POD（PML致癌结构域）中的亚细胞分布。SuPr-1还改变了其他与核POD相关的蛋白质的分布，如作为转录调节因子的CBP和Daxx。PML增强了SuPr-1对转录的作用，并且SuPr-1在缺乏PML的成纤维细胞中无法激活转录。我们的研究确立了SUMO蛋白酶在转录中的重要作用。
