scholarly journals Cell cycle function of a Medicago sativa A2-type cyclin interacting with a PSTAIRE-type cyclin-dependent kinase and a retinoblastoma protein

2000 ◽  
Vol 23 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Francois Roudier ◽  
Elena Fedorova ◽  
Janos Gyorgyey ◽  
Attila Feher ◽  
Spencer Brown ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Medicago Sativa ◽  
Retinoblastoma Protein ◽  
Cyclin Dependent Kinase

scholarly journals The Cyclin-dependent Kinase Cdk2 Regulates Thymocyte Apoptosis

1999 ◽  
Vol 189 (6) ◽  
pp. 957-968 ◽  
Author(s):  
Anne Hakem ◽  
Takehiko Sasaki ◽  
Ivona Kozieradzki ◽  
Josef M. Penninger
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Retinoblastoma Protein ◽  
Cyclin Dependent Kinase ◽  
Tumor Suppressor P53 ◽  
Caspase Activation ◽  
Mitochondrial Permeability ◽  
Protein Inhibition ◽  
Cdk2 Activity ◽  
Thymocyte Apoptosis

Aberrant activation of cell cycle molecules has been postulated to play a role in apoptosis (“catastrophic cell cycle”). Here we show that in noncycling developing thymocytes, the cyclin- dependent kinase Cdk2 is activated in response to all specific and nonspecific apoptotic stimuli tested, including peptide-specific thymocyte apoptosis. Cdk2 was found to function upstream of the tumor suppressor p53, transactivation of the death promoter Bax, alterations of mitochondrial permeability, Bcl-2, caspase activation, and caspase-dependent proteolytic cleavage of the retinoblastoma protein. Inhibition of Cdk2 completely protected thymocytes from apoptosis, mitochondrial changes, and caspase activation. These data provide the first evidence that Cdk2 activity is crucial for the induction of thymocyte apoptosis.

Human lactoferrin controls the level of retinoblastoma protein and its activityThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 345-350 ◽  
Author(s):  
Hee-Joung Son ◽  
Shin-Hee Lee ◽  
Sang-Yun Choi
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Kinase Inhibitor ◽  
Peer Review Process ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein ◽  
Cyclin Dependent Kinase ◽  
Antiproliferative Effects ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Selection Of

Lactoferrin (Lf) has been implicated in the regulation of cell growth. However, the molecular mechanism underlying this effect remains to be elucidated. In this study, we show that Lf is involved in the cell cycle control system in a variety of cell lines, through retinoblastoma protein (Rb) - mediated growth arrest. We observed that Lf induces the expression of Rb, a signal mediator of cell cycle control, and that a majority of this Lf-induced Rb persists in a hypophosphorylated form. In addition, we determined that Lf specifically augments the level of a cyclin-dependent kinase inhibitor, p21, but not p27. Upon treatment with Lf, H1299 cells expressing defective p53 effected an augmentation of endogenous p21 levels, which may contribute to the accumulation of hypophosphorylated Rb. A substantial quantity of active Rb binds more efficiently to E2F1 in cells that express Lf and consequently blocks the expression of an E2F1-responsive gene, thereby suggesting that Lf plays a crucial role in the inhibition of tumor cell growth. Therefore, we conclude that the antiproliferative effects of Lf can likely be attributed to the elevated levels of hypophosphorylated Rb.

scholarly journals P21 and Retinoblastoma Protein Control the Absence of DNA Replication in Terminally Differentiated Muscle Cells

2000 ◽  
Vol 149 (2) ◽  
pp. 281-292 ◽  
Author(s):  
Asoke Mal ◽  
Debasis Chattopadhyay ◽  
Mrinal K. Ghosh ◽  
Randy Y.C. Poon ◽  
Tony Hunter ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Retinoblastoma Protein ◽  
Muscle Cells ◽  
Cyclin Dependent Kinase ◽  
Adenovirus E1a ◽  
Protein Levels ◽  
Quiescent Cells ◽  
Cdk2 Activity ◽  
Multinucleated Myotubes

During differentiation, skeletal muscle cells withdraw from the cell cycle and fuse into multinucleated myotubes. Unlike quiescent cells, however, these cells cannot be induced to reenter S phase by means of growth factor stimulation. The studies reported here document that both the retinoblastoma protein (Rb) and the cyclin-dependent kinase (cdk) inhibitor p21 contribute to this unresponsiveness. We show that the inactivation of Rb and p21 through the binding of the adenovirus E1A protein leads to the induction of DNA replication in differentiated muscle cells. Moreover, inactivation of p21 by E1A results in the restoration of cyclin E–cdk2 activity, a kinase made nonfunctional by the binding of p21 and whose protein levels in differentiated muscle cells is relatively low in amount. We also show that restoration of kinase activity leads to the phosphorylation of Rb but that this in itself is not sufficient for allowing differentiated muscle cells to reenter the cell cycle. All the results obtained are consistent with the fact that Rb is functioning downstream of p21 and that the activities of these two proteins may be linked in sustaining the postmitotic state.

scholarly journals Serum-Induced Expression of the cdc25AGene by Relief of E2F-Mediated Repression

1999 ◽  
Vol 19 (7) ◽  
pp. 4695-4702 ◽  
Author(s):  
Xi Chen ◽  
Ron Prywes
Keyword(s):  
Cell Cycle ◽  
Point Mutation ◽  
Kinase Activity ◽  
Tyrosine Phosphatase ◽  
Retinoblastoma Protein ◽  
Early Gene ◽  
Cyclin Dependent Kinase ◽  
3T3 Cells ◽  
Induced Expression ◽  
Nih 3T3

ABSTRACT The cdc25A gene encodes a tyrosine phosphatase which activates cyclin-dependent kinase activity in the G1 phase of the cell cycle. cdc25A RNA levels are induced from 3 to 6 h after serum induction of serum-starved NIH 3T3 cells, suggesting that the cdc25A gene is a delayed-early gene. Analysis of cdc25A promoter constructs showed that thecdc25A promoter is sufficient for serum induction. Surprisingly for a gene expressed in early to mid-G1, serum induction of the promoter requires an E2F site at position −62 in the promoter. Deletion or point mutation of the E2F site resulted in activation of expression in serum-starved cells and no further induction by serum treatment. E2F factors were found to bind to thecdc25A E2F site along with the retinoblastoma protein (Rb) family members p130 and p107. A shift in mobility of the E2F-p107 complex in extracts of cells induced for 6 h correlated with induction of cdc25A expression. These results suggest that serum induction of cdc25A expression is mediated by inactivation of p107 or p130, both of which repress transcription when bound to the promoter through E2F.

scholarly journals The Role of Cdh1p in Maintaining Genomic Stability in Budding Yeast

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 489-503 ◽  
Author(s):  
Karen E Ross ◽  
Orna Cohen-Fix
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Chromosome Loss ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Growth Defects ◽  
Genes Encoding ◽  
Specificity Factor

Abstract Cdh1p, a substrate specificity factor for the cell cycle-regulated ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), promotes exit from mitosis by directing the degradation of a number of proteins, including the mitotic cyclins. Here we present evidence that Cdh1p activity at the M/G1 transition is important not only for mitotic exit but also for high-fidelity chromosome segregation in the subsequent cell cycle. CDH1 showed genetic interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle assembly checkpoint that acts at metaphase to prevent premature chromosome segregation. Unlike cdh1Δ and mad2Δ single mutants, the mad2Δ cdh1Δ double mutant grew slowly and exhibited high rates of chromosome and plasmid loss. Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome missegregation and cell death. Our data suggest that at least part of the chromosome loss can be attributed to kinetochore/spindle problems. Our data further suggest that Cdh1p and Sic1p, a Cdc28p/Clb inhibitor, have overlapping as well as nonoverlapping roles in ensuring proper chromosome segregation. The severe growth defects of both mad2Δ cdh1Δ and pds1Δ cdh1Δ strains were rescued by overexpressing Swe1p, a G2/M inhibitor of the cyclin-dependent kinase, Cdc28p/Clb. We propose that the failure to degrade cyclins at the end of mitosis leaves cdh1Δ mutant strains with abnormal Cdc28p/Clb activity that interferes with proper chromosome segregation.

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