Inhibition of c-Myc activity by ribosomal protein L11

Dai, Mu Shui; Arnold, Hugh; Sun, Xiao Xin; Sears, Rosalie C.; Lu, Hua

doi:10.1038/emboj.2009.70

Cited by 60 publications

(127 citation statements)

References 42 publications

(66 reference statements)

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“…2 Further interrogating this in a more physiological setting would offer more insight into how these RPs play roles in cancer development and cancer prevention. Because more RPs have been found to activate p53, but inactivate c-Myc, 46,[52][53][54] our findings together with others 28,29 not only strengthen the notion that some RPs, such as RPL5, RPL11 and RPS14, possess intrinsic extra-ribosome functions in regulating other important cancer-relevant protein molecules, but also emphasize their potential roles as tumor suppressors.…”

Section: Discussionsupporting

confidence: 79%

“…The Flag-tagged RPL5, RPL11, RPS14, RPL30, RPS12, RPS19 and RPS27a, HA-MDM2, TAp73, GFP-TAp73, and Myc-ΔNp73 mammalian expression plasmids and the His-tagged RPL5, RPL11 and MDM2, and GST-TAp73 plasmid for bacterial expression was described previously. 15,18,26,27,52 The V5-tagged p53 plasmid was purchased from Addgene. Anti-RPL5, 18 anti-RPL11, 52 anti-HA (12CA5), anti-MDM2 (2A10 and 4B11) 18 Cell culture.…”

Section: Methodsmentioning

confidence: 99%

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Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition

et al. 2014

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Over the past decade, a number of ribosomal proteins (RPs) have been found to have a role in activating the tumor suppressor p53 by directly binding to MDM2 and impeding its activity toward p53. Herein, we report that RPL5 and RPL11 can also enhance the transcriptional activity of a p53 homolog TAp73, but through a distinct mechanism. Interestingly, even though RPL5 and RPL11 were not shown to bind to p53, they were able to directly associate with the transactivation domain of TAp73 independently of MDM2 in response to RS. This association led to perturbation of the MDM2-TAp73 interaction, consequently preventing MDM2 from its association with TAp73 target gene promoters. Furthermore, ectopic expression of RPL5 or RPL11 markedly induced TAp73 transcriptional activity by antagonizing MDM2 suppression. Conversely, ablation of either of the RPs compromised TAp73 transcriptional activity, as evident by the reduction of p21 and Puma expression, in response to 5-fluorouracil (5-FU). Consistently, overexpression of RPL5 or RPL11 enhanced, but knockdown of either of them hampered, TAp73-mediated apoptosis. Intriguingly, simultaneous knockdown of TAp73 and either of the RPs was required for rescuing the 5-FU-triggered S-phase arrest of p53-null tumor cells. These results demonstrate a novel mechanism underlying the inhibition of tumor cell proliferation and growth by these two RPs via TAp73 activation.

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Section: Discussionsupporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition

et al. 2014

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“…However, these effects are p53 independent, indicating that additional pathways controlled by RPL11 are involved in the MLN4924 biological response. For example, RPL11 controls the transcriptional activity of c-myc and cyclin expression 60,61,62 . Indeed, loss of RPL11 was shown to suppress cell proliferation, in the absence of cell cycle arrest, independently of p53 62 .…”

Section: Discussionmentioning

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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“…37 E2F1 promoter reporter was kindly provided by Dr. Mu-Shui Dai. 39 Mouse c-Myc plasmids were amplified using PCR and cloned into pcDNA3.1 with an HA tag at the N terminus. Point mutations and deletion mutants of c-Myc and REGγ were cloned using PCR-based standard cloning method.…”

Section: Discussionmentioning

confidence: 99%

Regulation of c-Myc protein stability by proteasome activator REGγ

Jiang

Pan

et al. 2014

Cell Death Differ

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-Myc is a key transcriptional factor that has a prominent role in cell growth, differentiation and tumor development. Its protein levels are tightly controlled by ubiquitin-proteasome pathway and frequently deregulated in various cancers. Here, we report that the 11S proteasomal activator REGγ is a novel regulator of c-Myc abundance in cells. We showed that overexpression of wild-type REGγ, but not inactive mutants including N151Y and G250S, significantly promoted the degradation of c-Myc. Depletion of REGγ markedly increased the protein stability of c-Myc. REGγ interacts with the C-terminal region of c-Myc and regulates c-Myc protein turnover. Functionally, REGγ negatively regulates c-Myc-mediated cell proliferation. Interestingly, depletion of the Drosophila Reg homolog (dReg) in developing wings induced the upregulation of Drosophila Myc, which contributes to cell death. Collectively, these results suggest that REGγ proteasome has a conserved role in the regulation of Myc abundance in both mammalian cells and Drosophila.

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Inhibition of c-Myc activity by ribosomal protein L11

Abstract: In page 3344, there is an error for the primers for L11 mRNA in paragraph under 'Reverse transcriptase-polymerase chain reaction and quantitative real-time PCR analysis'. The correct primers for L11 should be 5 0 -ATGGCGCAGGATCAAGGTG-3 0 and 5 0 -ATTT GCCAGGAAGGATG-3 0 .

Cited by 60 publications

References 42 publications

Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition

Ribosomal proteins L11 and L5 activate TAp73 by overcoming MDM2 inhibition

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

Regulation of c-Myc protein stability by proteasome activator REGγ

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