scholarly journals Ribosomal Protein L23 Activates p53 by Inhibiting MDM2 Function in Response to Ribosomal Perturbation but Not to Translation Inhibition

2004 ◽  
Vol 24 (17) ◽  
pp. 7654-7668 ◽  
Author(s):  
Mu-Shui Dai ◽  
Shelya X. Zeng ◽  
Yetao Jin ◽  
Xiao-Xin Sun ◽  
Larry David ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Ectopic Expression ◽  
Growth Control ◽  
Feedback Regulation ◽  
80S Ribosome ◽  
Translation Inhibition ◽  
P53 Activation ◽  
Stress Signals ◽  
Interfering Rna ◽  
Cell Growth Control

ABSTRACT The p53-MDM2 feedback loop is vital for cell growth control and is subjected to multiple regulations in response to various stress signals. Here we report another regulator of this loop. Using an immunoaffinity method, we purified an MDM2-associated protein complex that contains the ribosomal protein L23. L23 interacted with MDM2, forming a complex independent of the 80S ribosome and polysome. The interaction of L23 with MDM2 was enhanced by treatment with actinomycin D but not by gamma-irradiation, leading to p53 activation. This activation was inhibited by small interfering RNA against L23. Ectopic expression of L23 reduced MDM2-mediated p53 ubiquitination and also induced p53 activity and G1 arrest in p53-proficient U2OS cells but not in p53-deficient Saos-2 cells. These results reveal that L23 is another regulator of the p53-MDM2 feedback regulation.

scholarly journals UBE2M Drives Hepatocellular Cancer Progression as a p53 Negative Regulator by Binding to MDM2 and Ribosomal Protein L11

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4901
Author(s):  
Ju-Ha Kim ◽  
Ji Hoon Jung ◽  
Hyo-Jung Lee ◽  
Deok-Yong Sim ◽  
Eunji Im ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Cancer Progression ◽  
Hepg2 Cells ◽  
Ectopic Expression ◽  
Hepatocellular Cancer ◽  
Negative Regulator ◽  
Tissue Array ◽  
P53 Expression ◽  
P53 Activation ◽  
Ribosomal Protein L11

Though UBE2M, an E2 NEDD8-conjugating enzyme, is overexpressed in HepG2, Hep3B, Huh7 and PLC/PRF5 HCCs with poor prognosis by human tissue array and TCGA analysis, its underlying oncogenic mechanism remains unclear. Herein, UBE2M depletion suppressed viability and proliferation and induced cell cycle arrest and apoptosis via cleavages of PARP and caspase 3 and upregulation of p53, Bax and PUMA in HepG2, Huh7 and Hep3B cells. Furthermore, UBE2M depletion activated p53 expression and stability, while the ectopic expression of UBE2M disturbed p53 activation and enhanced degradation of exogenous p53 mediated by MDM2 in HepG2 cells. Interestingly, UBE2M binds to MDM2 or ribosomal protein L11, but not p53 in HepG2 cells, despite crosstalk between p53 and UBE2M. Consistently, the colocalization between UBE2M and MDM2 was observed by immunofluorescence. Notably, L11 was required in p53 activation by UBE2M depletion. Furthermore, UBE2M depletion retarded the growth of HepG2 cells in athymic nude mice along with elevated p53. Overall, these findings suggest that UBE2M promotes cancer progression as a p53 negative regulator by binding to MDM2 and ribosomal protein L11 in HCCs.

scholarly journals Perturbation of 60 S Ribosomal Biogenesis Results in Ribosomal Protein L5- and L11-dependent p53 Activation

2010 ◽  
Vol 285 (33) ◽  
pp. 25812-25821 ◽  
Author(s):  
Xiao-Xin Sun ◽  
Yue-Gang Wang ◽  
Dimitris P. Xirodimas ◽  
Mu-Shui Dai
Keyword(s):  
Ribosomal Protein ◽  
Ribosomal Biogenesis ◽  
P53 Activation ◽  
Ribosomal Protein L5

scholarly journals A new twist on cell growth control

Cell Cycle ◽  
2014 ◽  
Vol 13 (22) ◽  
pp. 3474-3475 ◽  
Author(s):  
Joseph F Cardiello ◽  
Jennifer F Kugel ◽  
James A Goodrich
Keyword(s):  
Cell Growth ◽  
Growth Control ◽  
Cell Growth Control

scholarly journals Developmentally regulated GTPases: structure, function and roles in disease

2021 ◽  
Author(s):  
Christian A. E. Westrip ◽  
Qinqin Zhuang ◽  
Charlotte Hall ◽  
Charlotte D. Eaton ◽  
Mathew L. Coleman
Keyword(s):  
Cell Proliferation ◽  
Structural Biology ◽  
Regulatory Protein ◽  
Growth Control ◽  
Developmentally Regulated ◽  
Binding Partner ◽  
Cellular Processes ◽  
Gtp Binding ◽  
Evolutionarily Conserved ◽  
Cell Growth Control

AbstractGTPases are a large superfamily of evolutionarily conserved proteins involved in a variety of fundamental cellular processes. The developmentally regulated GTP-binding protein (DRG) subfamily of GTPases consists of two highly conserved paralogs, DRG1 and DRG2, both of which have been implicated in the regulation of cell proliferation, translation and microtubules. Furthermore, DRG1 and 2 proteins both have a conserved binding partner, DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively, that prevents them from being degraded. Similar to DRGs, the DFRP proteins have also been studied in the context of cell growth control and translation. Despite these proteins having been implicated in several fundamental cellular processes they remain relatively poorly characterized, however. In this review, we provide an overview of the structural biology and biochemistry of DRG GTPases and discuss current understanding of DRGs and DFRPs in normal physiology, as well as their emerging roles in diseases such as cancer.

Bacterial activation of β-catenin signaling in human epithelia

2004 ◽  
Vol 287 (1) ◽  
pp. G220-G227 ◽  
Author(s):  
Jun Sun ◽  
Michael E. Hobert ◽  
Anjali S. Rao ◽  
Andrew S. Neish ◽  
James L. Madara
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Transcriptional Activation ◽  
Growth Control ◽  
Effector Protein ◽  
Epithelial Cell Proliferation ◽  
Gut Flora ◽  
T Cell Factor ◽  
Mucosal Lining ◽  
Cell Growth Control

The mucosal lining of the human intestine is constantly bathed in a milieu of commensal gut flora, the vast majority of these being nonpathogenic microorganisms. Here, we demonstrate that microbial-epithelial cell interactions not only affect proinflammatory pathways but also influence β-catenin signaling, a key component in regulating epithelial cell proliferation. The nonpathogenic Salmonella strain PhoPc activates the β-catenin signaling pathway of human epithelia via a blockade of β-catenin degradation. Normal β-catenin ubiquitination necessary for constitutive β-catenin degradation is abolished, allowing the accumulation and translocation of β-catenin to the nucleus. Transcriptional activation mediated by the β-catenin/T cell factor complex increases c-myc expression and enhances cell proliferation. We also show that the Salmonella effector protein AvrA is involved in modulating this β-catenin activation. These data suggest that nonvirulent bacterial-epithelial interactions can influence β-catenin signaling and cell growth control in a manner previously unsuspected.

Lysozyme-dependent Proliferation Switch: Hematopoietic and Hybridoma Cell Growth Control with the Use of Antibody/GP130 Chimera

2002 ◽  
pp. 337-341
Author(s):  
Masahiro Kawahara ◽  
Akito Natsume ◽  
Satoshi Terada ◽  
Koichi Kato ◽  
Kouhei Tsumoto ◽  
...  
Keyword(s):  
Cell Growth ◽  
Growth Control ◽  
Cell Growth Control
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