scholarly journals Thiazolidinediones Modulate the Expression of β-Catenin and Other Cell-Cycle Regulatory Proteins by Targeting the F-Box Proteins of Skp1-Cul1-F-box Protein E3 Ubiquitin Ligase Independently of Peroxisome Proliferator-Activated Receptor γ

2007 ◽  
Vol 72 (3) ◽  
pp. 725-733 ◽  
Author(s):  
Shuo Wei ◽  
Li-Fang Lin ◽  
Chih-Cheng Yang ◽  
Yu-Chieh Wang ◽  
Geen-Dong Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Regulatory Proteins ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Cycle Regulatory Proteins ◽  
F Box Protein

scholarly journals The SCFSlimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication

2009 ◽  
Vol 184 (2) ◽  
pp. 225-239 ◽  
Author(s):  
Gregory C. Rogers ◽  
Nasser M. Rusan ◽  
David M. Roberts ◽  
Mark Peifer ◽  
Stephen L. Rogers
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Genomic Stability ◽  
Ubiquitin Ligases ◽  
S Phase ◽  
Proteolytic Degradation ◽  
Centriole Duplication ◽  
F Box Protein

Restricting centriole duplication to once per cell cycle is critical for chromosome segregation and genomic stability, but the mechanisms underlying this block to reduplication are unclear. Genetic analyses have suggested an involvement for Skp/Cullin/F box (SCF)-class ubiquitin ligases in this process. In this study, we describe a mechanism to prevent centriole reduplication in Drosophila melanogaster whereby the SCF E3 ubiquitin ligase in complex with the F-box protein Slimb mediates proteolytic degradation of the centrosomal regulatory kinase Plk4. We identified SCFSlimb as a regulator of centriole duplication via an RNA interference (RNAi) screen of Cullin-based ubiquitin ligases. We found that Plk4 binds to Slimb and is an SCFSlimb target. Both Slimb and Plk4 localize to centrioles, with Plk4 levels highest at mitosis and absent during S phase. Using a Plk4 Slimb-binding mutant and Slimb RNAi, we show that Slimb regulates Plk4 localization to centrioles during interphase, thus regulating centriole number and ensuring the block to centriole reduplication.

scholarly journals Structure-Based Virtual Screening and Biological Evaluation of Peptide Inhibitors for Polo-Box Domain

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 107 ◽  
Author(s):  
Fang Yan ◽  
Guangmei Liu ◽  
Tingting Chen ◽  
Xiaochen Fu ◽  
Miao-Miao Niu
Keyword(s):  
Cell Cycle ◽  
Virtual Screening ◽  
Fold Increase ◽  
Pharmacophore Modeling ◽  
Biological Evaluation ◽  
Peptide Inhibitors ◽  
Regulatory Proteins ◽  
Competitive Binding Assay ◽  
M Phase ◽  
Cell Cycle Regulatory Proteins

The polo-box domain of polo-like kinase 1 (PLK1-PBD) is proved to have crucial roles in cell proliferation. Designing PLK1-PBD inhibitors is challenging due to their poor cellular penetration. In this study, we applied a virtual screening workflow based on a combination of structure-based pharmacophore modeling with molecular docking screening techniques, so as to discover potent PLK1-PBD peptide inhibitors. The resulting 9 virtual screening peptides showed affinities for PLK1-PBD in a competitive binding assay. In particular, peptide 5 exhibited an approximately 100-fold increase in inhibitory activity (IC50 = 70 nM), as compared with the control poloboxtide. Moreover, cell cycle experiments indicated that peptide 5 effectively inhibited the expression of p-Cdc25C and cell cycle regulatory proteins by affecting the function of PLK1-PBD, thereby inducing mitotic arrest at the G2/M phase. Overall, peptide 5 can serve as a potent lead for further investigation as PLK1-PBD inhibitors.

scholarly journals Association of the Cell Cycle Regulatory Proteins p45SKP2and CksHs1

2001 ◽  
Vol 276 (27) ◽  
pp. 25030-25036 ◽  
Author(s):  
Lı́dia Mongay ◽  
Susana Plaza ◽  
Elena Vigorito ◽  
Carles Serra-Pagès ◽  
Jordi Vives
Keyword(s):  
Cell Cycle ◽  
Regulatory Proteins ◽  
Cell Cycle Regulatory Proteins

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival

2001 ◽  
Vol 194 (4) ◽  
pp. 436-443 ◽  
Author(s):  
Mohamed A. Elkablawy ◽  
Perry Maxwell ◽  
Kate Williamson ◽  
Neil Anderson ◽  
Peter W. Hamilton
Keyword(s):  
Cell Cycle ◽  
Colorectal Carcinoma ◽  
Patient Survival ◽  
Regulatory Proteins ◽  
Tumour Stage ◽  
Cell Cycle Regulatory Proteins

Effects ofHelicobacter pylori infection on cell cycle progression and the expression of cell cycle regulatory proteins

2004 ◽  
Vol 200 (3) ◽  
pp. 334-342 ◽  
Author(s):  
Antonio De Luca ◽  
Maria De Falco ◽  
Salvatore Iaquinto ◽  
Gaetano Iaquinto
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Regulatory Proteins ◽  
Cycle Progression ◽  
Cell Cycle Regulatory Proteins

scholarly journals PPARγ Activation Inhibits Growth and Survival of Human Endometriotic Cells by Suppressing Estrogen Biosynthesis and PGE2 Signaling.

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4803-4813 ◽  
Author(s):  
Dan I. Lebovic ◽  
Shahryar K. Kavoussi ◽  
JeHoon Lee ◽  
Sakhila K. Banu ◽  
Joe A. Arosh
Keyword(s):  
Cell Cycle ◽  
Stromal Cells ◽  
Cell Cycle Regulation ◽  
Chronic Inflammatory Disease ◽  
Reproductive Age ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Growth And Survival ◽  
Cycle Regulation ◽  
Estrogen Biosynthesis

Endometriosis is a chronic inflammatory disease of reproductive age women leading to chronic pelvic pain and infertility. Current antiestrogen therapies are temporizing measures, and endometriosis often recurs. Potential nonestrogenic or nonsteroidal targets are needed for treating endometriosis. Peroxisome proliferator-activated receptor (PPAR)γ, a nuclear receptor, is activated by thiazolidinediones (TZDs). In experimental endometriosis, TZDs inhibit growth of endometriosis. Clinical data suggest potential use of TZDs for treating pain and fertility concurrently in endometriosis patients. Study objectives were to 1) determine the effects of PPARγ action on growth and survival of human endometriotic epithelial and stromal cells and 2) identify the underlying molecular links between PPARγ activation and cell cycle regulation, apoptosis, estrogen biosynthesis, and prostaglandin E2 biosynthesis and signaling in human endometriotic epithelial and stromal cells. Results indicate that activation of PPARγ by TZD ciglitazone 1) inhibits growth of endometriotic epithelial cells 12Z up to 35% and growth of endometriotic stromal cells 22B up to 70% through altered cell cycle regulation and intrinsic apoptosis, 2) decreases expression of PGE2 receptors (EP)2 and EP4 mRNAs in 12Z and 22B cells, and 3) inhibits expression and function of P450 aromatase mRNA and protein and estrone production in 12Z and 22B cells through EP2 and EP4 in a stromal-epithelial cell-specific manner. Collectively, these results indicate that PGE2 receptors EP2 and EP4 mediate actions of PPARγ by incorporating multiple cell signaling pathways. Activation of PPARγ combined with inhibition of EP2 and EP4 may emerge as novel nonsteroidal therapeutic targets for endometriosis-associated pain and infertility, if clinically proven safe and efficacious.

Expression and modulation of map kinases and cell cycle regulatory proteins during pancreas regeneration

1998 ◽  
Vol 114 ◽  
pp. A450
Author(s):  
J. Cristobal Aliaga ◽  
E. Calvo ◽  
J. Morisset ◽  
N. Rivard
Keyword(s):  
Cell Cycle ◽  
Map Kinases ◽  
Regulatory Proteins ◽  
Pancreas Regeneration ◽  
Cell Cycle Regulatory Proteins

Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis

2000 ◽  
Vol 278 (4) ◽  
pp. F515-F529 ◽  
Author(s):  
Stuart J. Shankland ◽  
Gunter Wolf
Keyword(s):  
Cell Cycle ◽  
Renal Function ◽  
Renal Disease ◽  
Cell Injury ◽  
Critical Role ◽  
Regulatory Proteins ◽  
Specific Cell ◽  
Cell Cycle Proteins ◽  
Proliferation And Apoptosis ◽  
Cell Cycle Regulatory Proteins

The response to glomerular and tubulointerstitial cell injury in most forms of renal disease includes changes in cell number (proliferation and apoptosis) and cell size (hyerptrophy). These events typically precede and may be reponsible for the accumulation of extracellular matrix proteins that leads to a decrease in renal function. There is increasing evidence showing that positive (cyclins and cyclin-dependent kinases) and negative (cyclin-dependent kinase inhibitors) cell cycle regulatory proteins have a critical role in regulating these fundamental cellular responses to immune and nonimmune forms of injury. Data now show that altering specific cell cycle proteins affects renal cell proliferation and improves renal function. Equally exciting is the expanding body of literature showing novel biological roles for cell cycle proteins in the regulation of cell hypertrophy and apoptosis. With increasing understanding of the role for cell cyle regulatory proteins in renal disease comes the hope for potential therapeutic inverventions.

scholarly journals Hect E3 ubiquitin ligase Tom1 controls Dia2 degradation during the cell cycle

2012 ◽  
Vol 23 (21) ◽  
pp. 4203-4211 ◽  
Author(s):  
Dong-Hwan Kim ◽  
Deanna M. Koepp
Keyword(s):  
Cell Cycle ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
S Phase ◽  
Temperature Sensitive ◽  
Dependent Manner ◽  
Charged Residues ◽  
Phase Progression ◽  
Positively Charged

The ubiquitin proteasome system plays a pivotal role in controlling the cell cycle. The budding yeast F-box protein Dia2 is required for genomic stability and is targeted for ubiquitin-dependent degradation in a cell cycle–dependent manner, but the identity of the ubiquitination pathway is unknown. We demonstrate that the Hect domain E3 ubiquitin ligase Tom1 is required for Dia2 protein degradation. Deletion of DIA2 partially suppresses the temperature-sensitive phenotype of tom1 mutants. Tom1 is required for Dia2 ubiquitination and degradation during G1 and G2/M phases of the cell cycle, whereas the Dia2 protein is stabilized during S phase. We find that Tom1 binding to Dia2 is enhanced in G1 and reduced in S phase, suggesting a mechanism for this proteolytic switch. Tom1 recognizes specific, positively charged residues in a Dia2 degradation/NLS domain. Loss of these residues blocks Tom1-mediated turnover of Dia2 and causes a delay in G1–to–S phase progression. Deletion of DIA2 rescues a delay in the G1–to–S phase transition in the tom1Δ mutant. Together our results suggest that Tom1 targets Dia2 for degradation during the cell cycle by recognizing positively charged residues in the Dia2 degradation/NLS domain and that Dia2 protein degradation contributes to G1–to–S phase progression.

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