scholarly journals MyoD induced cell cycle arrest is associated with increased nuclear affinity of the Rb protein.

1993 ◽  
Vol 4 (7) ◽  
pp. 705-713 ◽  
Author(s):  
A M Thorburn ◽  
P A Walton ◽  
J R Feramisco
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Dna Synthesis ◽  
Cell Cycle Arrest ◽  
S Phase ◽  
Tumor Suppressor Protein ◽  
G1 Phase ◽  
Induced Expression ◽  
Rb Protein ◽  
Cycle Arrest

In studying the mechanism through which the myogenic determination protein MyoD prevents entry into the S phase of the cell cycle, we have found a relationship between MyoD and the retinoblastoma (Rb) tumor suppressor protein. By direct needle microinjection of purified recombinant MyoD protein into quiescent fibroblasts, which were then induced to proliferate by serum, we found that MyoD arrested progression of the cell cycle, in agreement with studies utilizing expression constructs for MyoD. By studying temporal changes in cells injected with MyoD protein, it was found that MyoD did not prevent serum induced expression of the protooncogene c-Fos, an event that occurs in the G0 to G1 transition of the cycle. Injection of the MyoD protein as late as 8 h after the addition of serum still caused an inhibition in DNA synthesis, suggesting that MyoD inhibits the G1 to S transition as opposed to the G0 to G1 transition. MyoD injection did not prevent the expression of cyclin A. However MyoD injection did result in a block in the increase in Rb extractibility normally seen in late G1 phase cells. As this phenomenon is associated with the hyperphosphorylation of Rb at this point in the cell cycle and is correlated with progression into S phase, this provides further evidence that MyoD blocks the cycle late in G1.

scholarly journals mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein.

1996 ◽  
Vol 16 (5) ◽  
pp. 2445-2452 ◽  
Author(s):  
J Chen ◽  
X Wu ◽  
J Lin ◽  
A J Levine
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Biological Activities ◽  
Tumor Suppressor Protein ◽  
G1 Arrest ◽  
Physical Interaction ◽  
P53 Tumor Suppressor ◽  
Cycle Arrest ◽  
P53 Tumor Suppressor Protein

The mdm-2 gene encodes a 90-kDa polypeptide that binds specifically to the p53 tumor suppressor protein. This physical interaction results in the inhibition of the transcriptional functions of p53 (J. Chen, J. Lin, and A. J. Levine, Mol. Med. 1:142-152, 1995, and J. Momand, G. P. Zambetti, D. C. Olson, D. George, and A. J. Levine, Cell 69:1237-1245, 1992). Experiments are described that demonstrate the ability of mdm-2 to abrogate both the p53-mediated cell cycle arrest and the apoptosis functions. In addition, the results presented here suggest that mdm-2 binding to p53 and the resultant inhibition of p53 transcription functions are critical for reversing p53-mediated cell cycle arrest. The N-terminal half or domain of the mdm-2 protein is sufficient to regulate these biological activities of p53, consistent with the possibility that the highly conserved central acidic region and the C-terminal putative zinc fingers of mdm-2 may encode other functions.

scholarly journals Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest

2020 ◽  
Vol 21 (9) ◽  
pp. 3227 ◽  
Author(s):  
Chia-Yu Wu ◽  
Chun-Hao Chan ◽  
Navneet Kumar Dubey ◽  
Hong-Jian Wei ◽  
Jui-Hua Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Small Cell ◽  
G1 Phase ◽  
Small Cell Lung ◽  
Cycle Arrest ◽  
Novel Therapeutic

Cancer pathogenesis results from genetic alteration-induced high or low transcriptional programs, which become highly dependent on regulators of gene expression. However, their role in progressive regulation of non-small-cell lung cancer (NSCLC) and how these dependencies may offer opportunities for novel therapeutic options remain to be understood. Previously, we identified forkhead box F1 (FOXF1) as a reprogramming mediator which leads to stemnesss when mesenchymal stem cells fuse with lung cancer cells, and we now examine its effect on lung cancer through establishing lowly and highly expressing FOXF1 NSCLC engineered cell lines. Higher expression of FOXF1 was enabled in cell lines through lentiviral transduction, and their viability, proliferation, and anchorage-dependent growth was assessed. Flow cytometry and Western blot were used to analyze cellular percentage in cell-cycle phases and levels of cellular cyclins, respectively. In mice, tumorigenic behavior of FOXF1 was investigated. We found that FOXF1 was downregulated in lung cancer tissues and cancer cell lines. Cell proliferation and ability of migration, anchorage-independent growth, and transformation were inhibited in H441-FOXF1H and H1299-FOXF1H, with upregulated tumor suppressor p21 and suppressed cellular cyclins, leading to cell-cycle arrest at the gap 1 (G1) phase. H441-FOXF1H and H1299-FOXF1H injected mice showed reduced tumor size. Conclusively, highly expressing FOXF1 inhibited NSCLC growth via activating tumor suppressor p21 and G1 cell-cycle arrest, thus offering a potentially novel therapeutic strategy for lung cancer.

scholarly journals Cyclin A Is a Functional Target of Retinoblastoma Tumor Suppressor Protein-mediated Cell Cycle Arrest

1999 ◽  
Vol 274 (39) ◽  
pp. 27632-27641 ◽  
Author(s):  
Karen E. Knudsen ◽  
Anne F. Fribourg ◽  
Matthew W. Strobeck ◽  
Jean-Marie Blanchard ◽  
Erik S. Knudsen
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Cyclin A ◽  
Tumor Suppressor Protein ◽  
Retinoblastoma Tumor Suppressor Protein ◽  
Retinoblastoma Tumor Suppressor ◽  
Cycle Arrest ◽  
Retinoblastoma Tumor

scholarly journals Recent Advances in p53

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 211
Author(s):  
Gabriella D’Orazi
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Transcription Factor ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Tumor Suppressor Protein ◽  
Cellular Functions ◽  
Tumor Suppressor Protein P53 ◽  
Cycle Arrest ◽  
Stress Signals

Tumor suppressor protein p53 (TP53) is a key transcription factor that, in response to various stress signals, regulates numerous genes involved in a broad range of cellular functions including DNA repair, apoptosis, cell cycle arrest, senescence, metabolism, etc [...]

scholarly journals Poly(ADP-ribose) Polymerase Activity Prevents Signaling Pathways for Cell Cycle Arrest after DNA Methylating Agent Exposure

2005 ◽  
Vol 280 (16) ◽  
pp. 15773-15785 ◽  
Author(s):  
Julie K. Horton ◽  
Donna F. Stefanick ◽  
Jana M. Naron ◽  
Padmini S. Kedar ◽  
Samuel H. Wilson
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Cell Cycle Arrest ◽  
Signaling Pathways ◽  
Dna Polymerase ◽  
S Phase ◽  
Dna Polymerase Β ◽  
Cycle Arrest ◽  
Parp Activity ◽  
Inhibition Of Dna Synthesis

Mouse fibroblasts, deficient in DNA polymerase β, are hypersensitive to monofunctional DNA methylating agents such as methyl methanesulfonate (MMS). Both wild-type and, in particular, repair-deficient DNA polymerase β null cells are highly sensitized to the cytotoxic effects of MMS by 4-amino-1,8-naphthalimide (4-AN), an inhibitor of poly(ADP-ribose) polymerase (PARP) activity. Experiments with synchronized cells suggest that exposure during S-phase of the cell cycle is required for the 4-AN effect. 4-AN elicits a similar extreme sensitization to the thymidine analog, 5-hydroxymethyl-2′-deoxyuridine, implicating the requirement for an intermediate of DNA repair. In PARP-1-expressing fibroblasts treated with a combination of MMS and 4-AN, a complete inhibition of DNA synthesis is apparent after 4 h, and by 24 h, all cells are arrested in S-phase of the cell cycle. Continuous incubation with 4-AN is required to maintain the cell cycle arrest. Caffeine, an inhibitor of the upstream checkpoint kinases ATM (ataxia telangiectasia-mutated) and ATR (ATM and Rad3-related), has no effect on the early inhibition of DNA synthesis, but cells are no longer able to maintain the block after 8 h. Instead, the addition of caffeine leads to arrest of cells in G2/M rather than S-phase after 24 h. Analysis of signaling pathways in cell extracts reveals an activation of Chk1 after treatment with MMS and 4-AN, which can be suppressed by caffeine. Our results suggest that inhibition of PARP activity results in sensitization to MMS through maintenance of an ATR and Chk1-dependent S-phase checkpoint.

Sign in / Sign up

Export Citation Format

Share Document