Topors Functions as an E3 Ubiquitin Ligase with Specific E2 Enzymes and Ubiquitinates p53

作者：Rajeev Rajendra, Diptee Malegaonkar, Pooja Pungaliya, Henderson Marshall, Zeshaan A. Rasheed, James E. Brownell, Leroy F. Liu, Stuart G. Lutzker, Ahamed Saleem, Eric H. Rubin · 发表于：Journal of Biological Chemistry · 年份：2004 · DOI：10.1074/jbc.c400300200 · 被引用次数：197 · 研究领域：Ubiquitin and proteasome pathways、Cancer-related Molecular Pathways、Epigenetics and DNA Methylation

The human topoisomerase I- and p53-binding protein topors contains a highly conserved, N-terminal C3HC4-type RING domain that is homologous to the RING domains of known E3 ubiquitin ligases. We demonstrate that topors functions in vitro as a RING-dependent E3 ubiquitin ligase with the E2 enzymes UbcH5a, UbcH5c, and UbcH6 but not with UbcH7, CDC34, or UbcH2b. Additional studies indicate that a conserved tryptophan within the topors RING domain is required for ubiquitination activity. Furthermore, both in vitro and cellular studies implicate p53 as a ubiquitination substrate for topors. Similar to MDM2, overexpression of topors results in a proteasome-dependent decrease in p53 protein expression in a human osteosarcoma cell line. These results are similar to the recent finding that a Drosophila topors orthologue ubiquitinates the Hairy transcriptional repressor and suggest that topors functions as a ubiquitin ligase for multiple transcription factors.