Regulation of p53 by the Ubiquitin-conjugating Enzymes UbcH5B/C in Vivo

Saville, Mark K.; Sparks, Alison; Xirodimas, Dimitris P.; Wardrop, J.; Stevenson, Lauren; Bourdon, Jean-Christophe; Woods, Yvonne L.; Lane, David P.

doi:10.1074/jbc.m403362200

Cited by 139 publications

(127 citation statements)

References 78 publications

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“…The cDNA was then used for quantitative real-time PCR (qRT-PCR) to monitor mdm2 expression. Primers for mdm2 (P2) promoter were previously described 63 . Full details can be found in supplementary information.…”

Section: Gene Expressionmentioning

confidence: 99%

The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway

et al. 2015

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The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway Bailly, A.; Perrin, A.; Bou Malhab, L. J.; Pion, E.; Larance, M.; Nagala, M.; Smith, P.; O'Donohue, M.-F.; Gleizes, P.-E.; Zomerdijk, Josephus; Lamond, Angus; Xirodimas, D. P. Published in: Oncogene DOI:10.1038/onc.2015.104 Publication date: 2016 Document VersionPeer reviewed version Link to publication in Discovery Research Portal Citation for published version (APA):Bailly, A., Perrin, A., Bou Malhab, L. J., Pion, E., Larance, M., Nagala, M., ... Xirodimas, D. P. (2016). The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway. Oncogene, 35(4), 415-426. DOI: 10.1038415-426. DOI: 10. /onc.2015 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain.• You may freely distribute the URL identifying the publication in the public portal. Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

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Section: Gene Expressionmentioning

confidence: 99%

The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway

et al. 2015

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“…In addition, the mRNA levels of Ube2d1 and Ube2d4 were reduced by Cd treatment for 3 hr, and those of Ube2d2 and Ube2d3 were suppressed after a 6 hr incubation. p53 accumulation in NRK-52E cells Saville et al (2004) showed that UbcH5B and UbcH5C (now called UBE2D2 and UBE2D3; the human orthologs of rodents Ube2d2 and Ube2d3, respectively) contribute to the ubiquitination and degradation of p53, tumor suppressor protein, in the human breast carcinoma cell line MCF7. Since Cd markedly suppressed the expression of all Ube2d genes (Fig.…”

Section: Cytotoxicity In Nrk-52e Cellsmentioning

confidence: 99%

Cadmium toxicity is caused by accumulation of p53 through the down-regulation of Ube2d family genes in vitro and in vivo

et al. 2011

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“…Even though UbcH1 is one of best characterized E2s (30, 31), few E3s are known to function with it (32,33). By itself UbcH1 forms anchorless Lys 48 Ub chains (30).…”

Section: Murf1 With Ubch1 (E2-25k) Forms a Homogeneous Lysmentioning

confidence: 99%

“…Because a Ub molecule contains seven lysines (Lys 6 , Lys 11 , Lys 27 , Lys 29 , Lys 33 , Lys 48 , and Lys 63 ), there are seven different possible types of isopeptide linkage. It is generally assumed that Ub chains contain only one type of isopeptide linkage (12)(13)(14), and that the nature of the Ub linkage determines the specific fate of the protein.…”

mentioning

confidence: 99%

Certain Pairs of Ubiquitin-conjugating Enzymes (E2s) and Ubiquitin-Protein Ligases (E3s) Synthesize Nondegradable Forked Ubiquitin Chains Containing All Possible Isopeptide Linkages

Kim

Lledı́as

et al. 2007

Journal of Biological Chemistry

386

407

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It is generally assumed that a specific ubiquitin ligase (E3)linksIn eukaryotic cells, ubiquitination serves to target regulatory and misfolded proteins for rapid degradation by proteasomes (1-3), to trigger endocytosis of membrane proteins (4), and also to allow specific protein-protein associations important in signal transduction, DNA repair, and gene transcription (5-8). Protein ubiquitination involves formation of isopeptide linkages between the C-terminal carboxyl group of a ubiquitin (Ub) 4 and an ⑀-amino group on a lysine on the protein substrate or a preceding Ub to form a polyUb chain. To synthesize such linkages, the C-terminal carboxyl group of a Ub is first activated by formation of a thioester bond with a cysteine on the Ubactivating enzyme (E1), and the activated Ub is then transferred as a thioester to one of the 20 -40 Ub-conjugating enzymes (E2) of the cell. The formation of a Ub chain on the substrate is then catalyzed by a Ub ligase (E3), which binds the substrate and an E2. Several families of E3s exist that differ in structure and mechanism. If ubiquitination is catalyzed by a member of the Ring finger or the U-box E3 family, the activated Ub is transferred from the E2 directly to a lysine on the protein substrate or to a preceding Ub. The abundant Ring finger and the related U-box families are small monomeric proteins that bind the substrate at one end and then in that vicinity release the reactive Ub from the E2-Ub thioester (9, 10). If ubiquitination is catalyzed by an E3 of the HECT domain family, the activated Ub is transferred from the E2 first to a cysteine on the E3 to form another thioester bond and then to the substrate or to a preceding Ub * This work was supported by grants from the NIGMS, the High Q Foundation, the Fund for Innovation from Elan Corp. (to A. L. G.), the National Institutes of Health (to S. P. G.), and National Institutes of Health R01 Grant GM65267 (to D. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 4 The abbreviations used are: Ub, ubiquitin; UPKn, ubiquitin peptide modified at lysine n by ubiquitination; Forked chain, Ub chain in which two Ub chains are linked to the adjacent lysines on the preceding Ub; E1, Ubactivating enzyme; E2, Ub-conjugating enzyme; E3, ubiquitin-protein isopeptide ligase; LC-MSMS liquid chromatography-tandem mass spectrometry; SIM, selective ion monitoring.

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Regulation of p53 by the Ubiquitin-conjugating Enzymes UbcH5B/C in Vivo

Cited by 139 publications

References 78 publications

The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway

The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway

Cadmium toxicity is caused by accumulation of p53 through the down-regulation of Ube2d family genes in vitro and in vivo

Certain Pairs of Ubiquitin-conjugating Enzymes (E2s) and Ubiquitin-Protein Ligases (E3s) Synthesize Nondegradable Forked Ubiquitin Chains Containing All Possible Isopeptide Linkages

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