Growth factors (GF) initiate and maintain transition through G1 to S phase. GF-dependence ends with phosphorylation of Rb by cyclin-dependent kinases (CDKs), enabling cells to pass through the restriction (R) point and to complete the remaining phases of the cell cycle. Cyclin D-dependent...

TGrowth factors (GF) initiate and maintain transition through G1 to S phase. GF-dependence ends with phosphorylation of Rb by cyclin-dependent kinases (CDKs), enabling cells to pass through the restriction (R) point and to complete the remaining phases of the cell cycle. Cyclin D-dependent kinase...

Cell cycle checkpoints constitute a network of signal transduction mechanisms to monitor DNA damage and regulate progression through the cell cycle. A series of events is triggered in cells upon DNA damage. Here we describe a framework for the understanding of the functions of the core components...

The p53 tumor suppressor protein plays a pivotal role in the cellular response to stress. A variety of stress signals trigger accumulation and activation of p53 to halt the cell cycle and to prevent replication of damaged DNA. The p53 protein is required for a proper G1 arrest, it is essential...

The onset of breast cancer in women is one of the most devastating diseases known today, afflicting approximately one in nine women in Western countries. In families that inherit breast and ovarian cancer, BRCA1 mutations account for close to 100% of resultant cancers, and in pedigrees that...

Tumor initiation is dependent on several key changes in the requirements for cell growth. Three of the most important features that distinguish transformed cells from untransformed cells are the loss of senescence, anchorage independent growth, and loss of contact inhibition. Cells that adopt a...

Over the past two decades, the basic molecular events controlling eukaryotic G2 to M-phase cell cycle transition have been deciphered. Studies in a variety of organisms have identified an evolutionarily conserved system for controlling mitotic onset through regulation of Cdc2 kinase activity....

Several decades of genetic and molecular study have revealed enormous insights into the mechanistic underpinnings of cancer. From the identification of dominantly acting oncogenes to the signaling pathways which modulate the cell cycle, our understanding of the machinery of cell cycle progression...

Chemotherapeutic drugs and radiation inhibit tumor cell proliferation by inducing growth arrest and cell death. The best-studied antiproliferative response to anticancer agents is programmed cell death or apoptosis. Inhibition of apoptosis, however, has been frequently found to have little or no...

Cyclin-dependent kinases (cdks) are core components of the cell cycle machinery. Orderly transition between cell cycle phases requires the scheduled activity of the cdks, governed in part by their associations with cyclins and cdk inhibitors, as well as by their state of phosphorylation. In...

There have emerged, within the aberrant cell cycle regulatory pathways frequently encountered in cancer cells, several potential targets for novel anticancer drug discovery. Cyclin-dependent kinases (CDKs) and their regulatory units, cyclins, play a central role in cell cycle progression, and...

Autocrine growth factor secretion by cells is a frequent event involved in malignant transformation. Constitutive growth factor gene expression can in turn result in the deregulation of survival. Furthermore, autocrine and paracrine growth factor synthesis can also contribute to the enhanced...

Tumor suppressor genes and oncogenes can be identified by positions of chromosomal translocations (in leukemia and lymphomas) and by detection of homozygous deletions and loss of heterozygosity (in solid tumors). Using these approaches, we identified a specific locus from the short arm of...

Checkpoints are mechanisms that establish dependence relationships between biochemically unrelated cellular processes. The temporal order of many critical cell cycle events must be strictly maintained to ensure cell survival and integrity. A simple example is that of genome duplication which must...