Wertz Ingrid E, O'Rourke Karen M, Zhang Zemin, Dornan David, Arnott David, Deshaies Raymond J, Dixit Vishva M
Department of Molecular Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
Science. 2004 Feb 27;303(5662):1371-4. doi: 10.1126/science.1093549. Epub 2004 Jan 22.
Arabidopsis thaliana De-etiolated-1 (AtDET1) is a highly conserved protein, with orthologs in vertebrate and invertebrate organisms. AtDET1 negatively regulates photomorphogenesis, but its biochemical mechanism and function in other species are unknown. We report that human DET1 (hDET1) promotes ubiquitination and degradation of the proto-oncogenic transcription factor c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1. Ablation of any subunit by RNA interference stabilized c-Jun and increased c-Jun-activated transcription. These findings characterize a c-Jun ubiquitin ligase and define a specific function for hDET1 in mammalian cells.
拟南芥去黄化-1（AtDET1）是一种高度保守的蛋白质，在脊椎动物和无脊椎动物中存在直系同源物。AtDET1负向调节光形态建成，但其在其他物种中的生化机制和功能尚不清楚。我们报道，人类DET1（hDET1）通过组装一种包含DNA损伤结合蛋白-1（DDB1）、Cullin 4A（CUL4A）、Cullins-1调节因子（ROC1）和组成型光形态建成-1的多亚基泛素连接酶，促进原癌基因转录因子c-Jun的泛素化和降解。通过RNA干扰去除任何一个亚基都会使c-Jun稳定，并增加c-Jun激活的转录。这些发现表征了一种c-Jun泛素连接酶，并确定了hDET1在哺乳动物细胞中的特定功能。
