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

Research output: Contribution to journalArticle

140 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

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Ubiquitin-Protein Ligases
Ubiquitination
Type I DNA Topoisomerase
Osteosarcoma
Proteasome Endopeptidase Complex
Enzymes
Ligases
Ubiquitin
Tryptophan
Drosophila
Carrier Proteins
Transcription Factors
Cells
Cell Line
Substrates
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Rajendra, R., Malegaonkar, D., Pungaliya, P., Marshall, H., Rasheed, Z., Brownell, J., ... 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

Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. / Rajendra, Rajeev; Malegaonkar, Diptee; Pungaliya, Pooja; Marshall, Henderson; Rasheed, Zeshaan; Brownell, James; Liu, Leroy-Fong; Lutzker, Stuart; Saleem, Ahamed; Rubin, Eric H.

In: Journal of Biological Chemistry, Vol. 279, No. 35, 27.08.2004, p. 36440-36444.

Research output: Contribution to journalArticle

Rajendra, R, Malegaonkar, D, Pungaliya, P, Marshall, H, Rasheed, Z, Brownell, J, Liu, L-F, Lutzker, S, Saleem, A & Rubin, EH 2004, 'Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53', Journal of Biological Chemistry, vol. 279, no. 35, pp. 36440-36444. https://doi.org/10.1074/jbc.C400300200
Rajendra R, Malegaonkar D, Pungaliya P, Marshall H, Rasheed Z, Brownell J et al. Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. Journal of Biological Chemistry. 2004 Aug 27;279(35):36440-36444. https://doi.org/10.1074/jbc.C400300200
Rajendra, Rajeev ; Malegaonkar, Diptee ; Pungaliya, Pooja ; Marshall, Henderson ; Rasheed, Zeshaan ; Brownell, James ; Liu, Leroy-Fong ; Lutzker, Stuart ; Saleem, Ahamed ; Rubin, Eric H. / Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 35. pp. 36440-36444.
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