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PMID:15247280

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Citation

Rajendra, R, Malegaonkar, D, Pungaliya, P, Marshall, H, Rasheed, Z, Brownell, J, Liu, LF, Lutzker, S, Saleem, A and Rubin, EH (2004) Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. J. Biol. Chem. 279:36440-4

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.

Links

PubMed Online version:10.1074/jbc.C400300200

Keywords

Amino Acid Sequence; Animals; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cell Line, Tumor; Cysteine Endopeptidases/metabolism; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; Drosophila; Electrophoresis, Polyacrylamide Gel; Glutathione Transferase/metabolism; Green Fluorescent Proteins; Humans; Immediate-Early Proteins/metabolism; Immunoblotting; Iron-Binding Proteins/chemistry; Luminescent Proteins/metabolism; Mass Spectrometry; Molecular Sequence Data; Multienzyme Complexes/metabolism; Neoplasm Proteins; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Plasmids/metabolism; Proteasome Endopeptidase Complex; Protein Structure, Tertiary; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-mdm2; Recombinant Proteins/chemistry; Sequence Homology, Amino Acid; Silver Staining; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transcription Factors/metabolism; Transcription Factors/physiology; Transcription, Genetic; Transfection; Tryptophan/chemistry; Tumor Suppressor Protein p53/metabolism; Ubiquitin/metabolism; Ubiquitin-Conjugating Enzymes/chemistry; Ubiquitin-Protein Ligase Complexes/biosynthesis; Ubiquitin-Protein Ligases/metabolism; Ubiquitin-Protein Ligases/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:UB2D1

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2D1

part_of

GO:0000151: ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:UB2D1

enables

GO:0061631: ubiquitin conjugating enzyme activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:P04637)

Seeded From UniProt

complete

HUMAN:UB2E1

enables

GO:0061631: ubiquitin conjugating enzyme activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:P04637)

Seeded From UniProt

complete

HUMAN:UB2D2

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2D2

part_of

GO:0000151: ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:UB2D2

enables

GO:0061631: ubiquitin conjugating enzyme activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:P04637)

Seeded From UniProt

complete

HUMAN:TOPRS

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:P04637)

Seeded From UniProt

complete

HUMAN:UB2E1

enables

GO:0061631: ubiquitin conjugating enzyme activity

ECO:0000314: direct assay evidence used in manual assertion

F

has_input:(UniProtKB:P04637)

Seeded From UniProt

complete

HUMAN:UB2E1

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UB2E1

part_of

GO:0000151: ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TOPRS

part_of

GO:0000151: ubiquitin ligase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TOPRS

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

has_direct_input:(UniProtKB:P04637)

Seeded From UniProt

complete

HUMAN:TOPRS

involved_in

GO:0006513: protein monoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TOPRS

involved_in

GO:0051443: positive regulation of ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TOPRS

involved_in

GO:0070936: protein K48-linked ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TOPRS

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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