Mitochondrial ribosomal protein L41 mediates serum starvation-induced cell-cycle arrest through an increase of p21WAF1/CIP1

2005 ◽  
Vol 338 (2) ◽  
pp. 1179-1184 ◽  
Author(s):  
Mi Jin Kim ◽  
Young A. Yoo ◽  
Hyung Jung Kim ◽  
Seongman Kang ◽  
Yong Geon Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ribosomal Protein ◽  
Cell Cycle Arrest ◽  
Serum Starvation ◽  
Mitochondrial Ribosomal Protein ◽  
Cycle Arrest

scholarly journals Mitochondrial Ribosomal Protein L41 Suppresses Cell Growth in Association with p53 and p27Kip1

2005 ◽  
Vol 25 (15) ◽  
pp. 6603-6616 ◽  
Author(s):  
Young A Yoo ◽  
Mi Jin Kim ◽  
Jong Kuk Park ◽  
Young Min Chung ◽  
Jong Hyeok Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
P53 Protein ◽  
Suppressive Effect ◽  
Serum Starvation ◽  
Mitochondrial Ribosomal Protein ◽  
Growth Inhibitory ◽  
Tumor Tissues ◽  
Induced Apoptosis

ABSTRACT The p53 protein arrests the cell cycle at the G1 phase when stabilized by the interaction between ribosomal proteins and HDM2 under growth-inhibitory conditions. Meanwhile, p53, when translocated to the mitochondria in response to cell death signals, induces apoptosis via transcription-independent mechanisms. In this report, we demonstrate that the mitochondrial ribosomal protein L41 (MRPL41) enhances p53 stability and contributes to p53-induced apoptosis in response to growth-inhibitory conditions such as actinomycin D treatment and serum starvation. An analysis of MRPL41 expression in paired normal and tumor tissues revealed lower expression in tumor tissue. Ectopic MRPL41 expression resulted in inhibition of the growth of cancer cells in tissue culture and tumor growth in nude mice. We discovered that MRPL41 protein is localized in the mitochondria, stabilizes the p53 protein, and enhances its translocation to the mitochondria, thereby inducing apoptosis. Interestingly, in the absence of p53, MRPL41 stabilizes the p27Kip1 protein and arrests the cell cycle at the G1 phase. These results suggest that MRPL41 plays an important role in p53-induced mitochondrion-dependent apoptosis and MRPL41 exerts a tumor-suppressive effect in association with p53 and p27 Kip1.

The Ribosomal Protein RPLP0 Mediates PLAAT4-induced Cell Cycle Arrest and Cell Apoptosis

2019 ◽  
Vol 77 (3) ◽  
pp. 253-260 ◽  
Author(s):  
Chun-Hua Wang ◽  
Lu-Kai Wang ◽  
Chang-Chieh Wu ◽  
Mao-Liang Chen ◽  
Ming-Cheng Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ribosomal Protein ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Cycle Arrest

Nucleolar Stress and p53 Mediated Erythroid Failure in Diamond Blackfan Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 42-42
Author(s):  
Colin Sieff ◽  
Harvey F. Lodish
Keyword(s):  
Cell Cycle ◽  
Ribosomal Protein ◽  
Cell Cycle Arrest ◽  
Ribosomal Rna ◽  
Mammalian Cells ◽  
Pcr Analysis ◽  
Erythroid Cells ◽  
Cycle Arrest ◽  
Nucleolar Stress ◽  
Primary Mouse

Abstract The discovery that several ribosomal protein genes can be mutated in DBA suggests that ribosomal protein gene mutations may account for many or all cases of DBA, and focuses attention on the ribosome. While experiments in yeast and mammalian cells show that RPS19 depletion or mutation leads to a block in ribosomal RNA biosynthesis, this result does not explain why erythropoiesis is so severely affected in DBA. We hypothesize that during fetal development immature erythroid cells proliferate more rapidly than other lineages and therefore require very high ribosome synthetic rates to generate sufficient capacity for translation of erythroid specific transcripts that must take place before these unique cells enucleate. To test this kinetic hypothesis we measured RNA biogenesis in primary mouse fetal liver cells and reported previously that during the first 24 hours cell number increases 3–4 fold while, remarkably, there is a 6-fold increase in RNA content during the same period, suggesting that the cells accumulate an excess of ribosomal RNA (80% of measured RNA) during early erythropoiesis. Retrovirus infected siRNA RPS19 knockdown cells show reduced proliferation of FACS sorted GFP positive cells at 48 hours. Although the cell yield is reduced, the differentiation pattern of the surviving GFP positive cells is similar to that of the controls. While quantitative RT-PCR analysis shows that RPS19 mRNA is rapidly depleted, Western analysis during this time course does not show a deficiency of RPS19 protein. This suggests strongly that the proliferative defect is not due to insufficiency of RPS19 protein, and is more likely due nucleolar stress induced by the block in ribosome biogenesis. Molecular consequences could lead to redistribution of cell cycle proteins normally resident in the nucleolus with consequent p53 mediated cell cycle arrest and or apoptosis. To test this hypothesis we used a culture system that allows expansion without differentiation of immature cells in SCF, EPO, IGF-1 and dexamethasone. Under these conditions proliferation of siRNA expressing precursors is reduced with an increased proportion arrested in G0/G1 in the knockdown cells. Furthermore, p53 is increased in the knockdown cells. Taken together, these data suggest that RPS19 insufficient cells undergo a nucleolar stress response and erythroid cells proliferate poorly because of p53 mediated cell cycle arrest and apoptosis.

scholarly journals Cell Cycle Arrest in G2/M Promotes Early Steps of Infection by Human Immunodeficiency Virus

2005 ◽  
Vol 79 (9) ◽  
pp. 5695-5704 ◽  
Author(s):  
Bettina Groschel ◽  
Frederic Bushman
Keyword(s):  
Cell Cycle ◽  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Cell Cycle Arrest ◽  
Lung Fibroblasts ◽  
Serum Starvation ◽  
Cycle Arrest ◽  
Immunodeficiency Virus ◽  
High Concentrations ◽  
Transformed Cell Lines

ABSTRACT We have identified four small molecules that boost transduction of cells by human immunodeficiency virus (HIV) and investigated their mechanism of action. These molecules include etoposide and camptothecin, which induce DNA damage by inhibiting religation of cleaved topoisomerase-DNA complexes, taxol, which interferes with the function of microtubules, and aphidicolin, which inhibits DNA polymerases. All four compounds arrest the cell cycle at G2/M, though in addition high concentrations of aphidicolin arrest in G1. We find that early events of HIV replication, including synthesis of late reverse transcription products, two-long terminal repeat circles, and integrated proviruses, were increased after treatment of cells with concentrations of each compound that arrested in G2/M. Stimulation was seen for both transformed cell lines (293T and HeLa cells) and primary cells (IMR90 lung fibroblasts). Arrest in G1 with high concentrations of aphidicolin boosted transduction, though not much as with lower concentrations that arrested in G2/M. Arrest of IMR90 cells in G1 by serum starvation and contact inhibition reduced transduction. Previously, the proteasome inhibitor MG132 was reported to increase HIV infection—here we investigated the effects of combinations of the cell cycle inhibitors with MG132 and obtained data suggesting that MG132 may also boost transduction by causing G2/M cell cycle arrest. These data document that cell cycle arrest in G2/M boosts the early steps of HIV infection and suggests methods for increasing transduction with HIV-based vectors.

scholarly journals Loss of RPS27a expression regulates cell cycle, apoptosis, and proliferation via the RPS27a-RPL11-MDM2-p53 pathway in lung adenocarcinoma cells

2021 ◽  
Author(s):  
Hongyan Li ◽  
Hong Zhang ◽  
Guomin Huang ◽  
Zhitong Bing ◽  
Hongtao Luo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
Ribosomal Protein ◽  
Cell Cycle Arrest ◽  
Complex Structure ◽  
Protein Docking ◽  
Stable Complex ◽  
P53 Expression ◽  
Cycle Arrest ◽  
Tcga Dataset

Abstract Background Some ribosomal proteins (RPs) might regulate the MDM2–p53 loop by binding to RPL5 or RPL11. This study aimed to explore whether ribosomal protein S27a (RPS27a) interacted with the ribosomal protein L11 (RPL11) to regulate p53 in lung adenocarcinoma (LUAD) cells. Methods RPL11-interacting proteins were identified using a proteomics approach. Co-immunoprecipitation (co-IP), docking analysis, GST-fusion and in vitro ubiquitination assay were used to analyze the interaction of RPS27a and RPL11. Cell cycle, apoptosis, cell invasion, cell viability and colony-formation assay were analyzed by knocking down RPS27a. The RPS27a mRNA expression in LUAD was analyzed based on the TCGA dataset and the RPS27a expression was detected by immunohistochemistry in LUAD samples. At last, the RPS27a and p53 expression were analyzed by immunohistochemistry in xenograft tumors by blocking RPS27a. Results The ablation of RPS27a inhibits murine double minute 2 (MDM2)-mediated p53 ubiquitination, induced G1/S cell cycle arrest and apoptosis, and inhibited the proliferation of LUAD cells. Also, it induced p53-dependent cell cycle arrest and RPL11-dependent p53 activation. The protein–protein docking results revealed that RPS27a and RPL11 formed a stable complex structure. The GST-fusion protein–protein association assay demonstrated that RPS27a bound to RPL11. The overexpressed RPS27a in LUAD was found to be correlated with a poorer prognosis based on the TCGA dataset. RPS27a expression was high in patients with LUAD. Blocking RPS27a increased p53, thus, suppressing cell proliferation and A549 xenograft growth in nude mice. Conclusions This study was novel in reporting that RPs bound to RPL11 to regulate the MDM2-p53 feedback loop, revealing that RPS27a plays an important function in LUAD growth. Hence, RPS27a might provide a diagnostic marker or therapeutic target for patients with LUAD.

The potential role of ribosomal protein S5 on cell cycle arrest and initiation of murine erythroleukemia cell differentiation

2008 ◽  
Vol 104 (4) ◽  
pp. 1477-1490 ◽  
Author(s):  
Christina N. Matragkou ◽  
Eleni T. Papachristou ◽  
Sotirios S. Tezias ◽  
Asterios S. Tsiftsoglou ◽  
Theodora Choli‐Papadopoulou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Differentiation ◽  
Ribosomal Protein ◽  
Cell Cycle Arrest ◽  
Potential Role ◽  
Cycle Arrest ◽  
Erythroleukemia Cell ◽  
Murine Erythroleukemia ◽  
Murine Erythroleukemia Cell

scholarly journals Impact of roscovitine, a selective CDK inhibitor, on cancer cells: bi-functionality increases its therapeutic potential.

2009 ◽  
Vol 56 (3) ◽  
Author(s):  
Józefa Wesierska-Gadek ◽  
Andreea Borza ◽  
Oxana Komina ◽  
Margarita Maurer
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
De Novo ◽  
Therapeutic Potential ◽  
Serum Starvation ◽  
Proliferative Potential ◽  
Cycle Arrest ◽  
Mcf 7

Increased expression and activity of proteins driving cell cycle progression as well as inactivation of endogenous inhibitors of cyclin-dependent kinases (CDKs) enhance the proliferative potential of cells. Escape of cells during malignant transformation from the proper cell cycle control rendering them independent from growth factors provides rationale for therapeutic targeting of CDKs. Exposure of rapidly growing human MCF-7 breast cancer and HeLa cervix cancer cells to roscovitine (ROSC), a selective inhibitor of CDKs, inhibits their proliferation by induction of cell cycle arrest and/or apoptosis. The outcome strongly depends on the intrinsic traits of the tumor cells, on their cell cycle status prior to the onset of treatment and also on ROSC concentration. At lower dose ROSC primarily inhibits the cell cycle-related CDKs resulting in a strong cell cycle arrest. Interestingly, ROSC arrests asynchronously growing cells at the G(2)/M transition irrespective of the status of their restriction checkpoint. However, the exposure of cancer cells synchronized after serum starvation in the late G(1) phase results in a transient G(1) arrest only in cells displaying the intact G(1)/S checkpoint. At higher dosage ROSC triggers apoptosis. In HeLa cells inhibition of the activity of CDK7 and, in consequence, that of RNA polymerase II is a major event that facilitates the initiation of caspase-dependent apoptosis. In contrast, in the caspase-3-deficient MCF-7 breast cancer cells ROSC induces apoptosis by a p53-dependent pathway. HIPK2-mediated activation of the p53 transcription factor by phosphorylation at Ser46 results in upregulation of p53AIP1 protein. This protein after de novo synthesis and translocation into the mitochondria promotes depolarization of the mitochondrial membrane.

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