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Viruses are obligate intracellular parasites that alter the environment of infected cells in order to replicate more efficiently. One way viruses achieve this is by modulating cell cycle progression. The main ...
Increasing knowledge on the cell cycle deregulations in cancers has promoted the introduction of phytochemicals, which can either modulate signaling pathways leading to cell cycle regulation or directly alter ...
The retinoblastoma protein, Rb, was one of the first tumor suppressor genes identified as a result of the familial syndrome retinoblastoma. In the period since its identification and cloning a large number of ...
Mitogenic induction of cyclin D1, the allosteric regulator of CDK4/6, is a key regulatory event contributing to G1 phase progression. Following the G1/S transition, cyclin D1 activation is antagonized by GSK3β...
The yeast SCFMet30 ubiquitin ligase plays a critical role in cell division by regulating the Met4 transcriptional activator of genes that control the uptake and assimilation of sulfur into methionine and S-adenos...
During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segreg...
Novel murine models of retinoblastoma based on Rb gene deletion in concert with inactivation of Rb family members have recently been developed. These new Rb knockout models of retinoblastoma provide excellent too...
Monoubiquitination of H2A is a major histone modification in mammalian cells. Understanding how monoubiquitinated H2A (uH2A) regulates DNA-based processes in the context of chromatin is a challenging question....
Cullin-RING ubiquitin ligases (CRLs) comprise the largest known category of ubiquitin ligases. CRLs regulate an extensive number of dynamic cellular processes, including multiple aspects of the cell cycle, tra...
The spindle checkpoint delays the onset of anaphase until all sister chromatids are aligned properly at the metaphase plate. To investigate the role san-1, the MAD3 homologue, has in Caenorhabditis elegans embryo...
SUMO proteins are small ubiquitin-like modifiers found in all eukaryotes that become covalently conjugated to other cellular proteins. The SUMO conjugation pathway is biochemically similar to ubiquitin conjuga...
Mammalian polo-like kinase 1 (Plk1) has been studied extensively as a critical element in regulating various mitotic events during M-phase progression. Plk1 function is spatially regulated through the targetin...
The cell cycle is tightly controlled to ensure that replication origins fire only once per cycle and that consecutive S-phases are separated by mitosis. When controls fail, DNA over-replication ensues: individ...
14-3-3 proteins are a family of adaptor proteins that participate in a wide variety of cellular processes. Recent evidence indicates that the expression levels of these proteins are elevated in some human tumo...
The basal-like breast cancer, a new category of breast cancer associated with poor prognosis and possibly unique chemosensitivity, is a current topic in the breast cancer field. Evidence from multiple sources ...
Problems with whole-culture synchronization methods for the study of the cell cycle have led to the need for an analysis of protein content during the cell cycle of cells that have not been starved or inhibite...
Biochemical analysis of the retinoblastoma protein's function has received considerable attention since it was cloned just over 20 years ago. During this time pRB has emerged as a key regulator of the cell div...
The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast ...
Considerable evidence has accumulated suggesting that cancer has genetic origin, based on the development of genomic alterations, such as deletions, mutations, and/or methylations in critical genes for homeost...
During mitosis, the genome duplicated during S-phase is synchronously and accurately segregated to the two daughter cells. The spindle checkpoint prevents premature sister-chromatid separation and mitotic exit...
Macrophage migration inhibitory factor (MIF) is a ubiquitously expressed pro-inflammatory mediator that has also been implicated in the process of oncogenic transformation and tumor progression. We used a gene...
Che-1 is a RNA polymerase II binding protein involved in the transcriptional regulation of E2F target genes and in cell proliferation. Recently, it has been shown that Che-1 accumulates in cells responding to ...
Membrane complement regulatory proteins (mCRPs) inhibit complement-mediated killing of human cells by human complement, a property that confers protection from complement to malignant breast cancer cells and t...
Completion of DNA replication before mitosis is essential for genome stability and cell viability. Cellular controls called checkpoints act as surveillance mechanisms capable of detecting errors and blocking c...
In eukaryotes, DNA replication is strictly regulated so that it occurs only once per cell cycle. The mechanisms that prevent excessive DNA replication are focused on preventing replication origins from being r...
In eukaryotic organisms, chromosomes are spatially organized within the nucleus. Such nuclear architecture provides a physical framework for the genetic activities of chromosomes, and changes its functional or...
Cyclin-dependent kinases (CDKs) regulate the progression of the cell cycle in eukaryotes. One of the major roles of CDK is to promote chromosomal DNA replication. However, how CDKs promote DNA replication has ...
DNA double strand breaks are efficiently repaired by homologous recombination. One of the last steps of this process is resolution of Holliday junctions that are formed at the sites of genetic exchange between...
Many meiosis-specific proteins in Schizosaccharomyces pombe contain coiled-coil motifs which play essential roles for meiotic progression. For example, the coiled-coil motifs present in Meu13 and Mcp7 are require...
The cyclin kinase inhibitor p27kip1 acts as a potent tumor supressor protein in a variety of human cancers. Its expression levels correlate closely with the overall prognosis of the affected patient and often pre...
Movement through the cell cycle is controlled by the temporally and spatially ordered activation of cyclin-dependent kinases paired with their respective cyclin binding partners. Cell cycle events occur in a s...
Ubiquitin is a highly versatile post-translational modification that controls virtually all types of cellular events. Over the past ten years we have learned that diverse forms of ubiquitin modifications and o...
The retinoblastoma (Rb) tumor suppressor gene product, pRb, has an established role in the implementation of cellular senescence, the state of irreversible G1 cell cycle arrest provoked by diverse oncogenic st...
In the quest for novel molecular mediators of glioma progression, we studied the regulation of FBXW 7 (hCDC 4/hAGO/SEL 10), its association with survival of patients with glioblastoma and its potential role as a ...
DNA replication must be tightly controlled to prevent initiation of a second round of replication until mitosis is complete. So far, components of the pre-replicative complex (Cdt1, Cdc6 and geminin) were cons...
The Fbw7 ubiquitin ligase promotes the rapid degradation of several important oncogenes, such as cyclin E, c-Myc, c-Jun, and Notch. The two fission yeast homologs of Fbw7, pop1 and pop2, have previously been s...
Haematopoietic cell number is maintained by a delicate balance between cell proliferation, differentiation and death. Gene knockout studies in mice have revealed the complex roles of cyclins, CDKs, and CDK inh...
Recent investigation of Cullin 4 (CUL4) has ushered this class of multiprotein ubiquitin E3 ligases to center stage as critical regulators of diverse processes including cell cycle regulation, developmental pa...
Oocytes from higher chordates, including man and nearly all mammals, arrest at metaphase of the second meiotic division before fertilization. This arrest is due to an activity that has been termed 'Cytostatic ...
"Natura non facit saltum" (nature makes no leap) the Latins used to say, meaning that nature does not like discontinuities. Cells make no exception and indeed any discontinuity in the DNA double helix is promp...
Cyclin D1 is an allosteric regulator for cyclin-dependent kinases 4 and 6 (CDK4/6). The cyclin D/CDK4 kinase promotes G1/S transition through the posttranslational modification and the subsequent inactivation ...
Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that functions as a modulator of signaling by the MAP kinase cascade. Implicated as a metastasis suppressor, Raf Kinase Inhibitory Pr...
We present evidence that variations in cyclin D1 levels through the cell cycle are essential for continuing proliferation. Cyclin D1 levels must be high during G1 phase for a cell to initiate DNA synthesis, bu...
Understanding how molecular motors generate force and move microtubules in mitosis is essential to understanding the physical mechanism of cell division. Recent measurements have shown that one mitotic kinesin...
Regulation of protein stability through the ubiquitin proteasome system is a key mechanism underlying numerous cellular processes. The ubiquitin protein ligases (or E3) are in charge of substrate specificity a...
Stem cells have recently attracted significant attention largely due to their potential therapeutic properties, but also because of their role in tumorigenesis and their resemblance, in many aspects, to cancer...
Proteins containing ubiquitin-like (UBL) and ubiquitin associated (UBA) domains have been suggested to shuttle ubiquitinated substrates to the proteasome for degradation. There are three UBL-UBA containing pro...
Abp1, and the closely related Cbh1 and Cbh2 are homologous to the human centromere-binding protein CENP-B that has been implicated in the assembly of centromeric heterochromatin. Fission yeast cells lacking Ab...
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