Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53

Rajeev Rajendra, Diptee Malegaonkar, Pooja Pungaliya, Henderson Marshall, Zeshaan Rasheed, James Brownell, Leroy-Fong Liu, Stuart Lutzker, Ahamed Saleem, Eric H. Rubin

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144 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)36440-36444
Number of pages5
JournalJournal of Biological Chemistry
Volume279
Issue number35
DOIs
Publication statusPublished - Aug 27 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Rajendra, R., Malegaonkar, D., Pungaliya, P., Marshall, H., Rasheed, Z., Brownell, J., Liu, L-F., Lutzker, S., Saleem, A., & Rubin, E. H. (2004). Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. Journal of Biological Chemistry, 279(35), 36440-36444. https://doi.org/10.1074/jbc.C400300200