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During neurogenesis, cell cycle regulators play a pivotal role in ensuring proper proliferation, cell cycle exit, and differentiation of neural precursors. However, the precise role of cyclin-dependent kinases (Cdks) in these processes is not well understood. We generated Cdk2 and Cdk4 double knockout (DKO) mice and found a striking ablation of the intermediate zone and cortical plate in mouse emb
Mammalian oocytes are arrested at the prophase of meiosis I during fetal or postnatal development, and the meiosis is resumed by the preovulatory surge of luteinizing hormone. The in vivo functional roles of cyclin-dependent kinases (Cdks) during the resumption of meiosis in mammalian oocytes are largely unknown. Previous studies have shown that deletions of Cdk3, Cdk4 or Cdk6 in mice result in vi
Cyclin-dependent kinase 1 (Cdk1) is an archetypical kinase and a central regulator that drives cells through G2 phase and mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo functions of Cdk1 have not been fully explored in mammals. Here we have generated a conditional-knockout mouse model to study the functions of Cdk1 in vivo. Ablation of Cdk1 leads to a
Orbital magnetization is known empirically to play an important role in several magnetic phenomena, such as permanent magnetism and ferromagnetic superconductivity. Within the recently developed "modern theory of orbital magnetization," theoretical insight has been gained into the nature of this often neglected contribution to magnetism but is based on an underlying mean-field approximation. From
Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorig
The recent Company of Biologists workshop 'Growth, Division and Differentiation: Understanding Developmental Control', which was held in September 2011 at Wiston House, West Sussex, UK, brought together researchers aiming to understand cell proliferation and differentiation in various metazoans, ranging from flies to mice. Here, we review the common themes that emerged from the meeting, highlighti
The identification of new members in the Cdk and cyclin families, functions for many of which are still emerging, has added new facets to the cell cycle regulatory network. With roles extending beyond the classical regulation of cell cycle progression, these new players are involved in diverse processes such as transcription, neuronal function, and ion transport. Members closely related to Cdks an
The concept of targeting G1 cyclin-dependent kinases (CDKs) in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues,
Comment on: Abdullah C, et al. Cell Cycle 2011; 10:977-88.
Terminal differentiation of mammalian erythroid progenitors involves 4-5 cell divisions and induction of many erythroid important genes followed by chromatin and nuclear condensation and enucleation. The protein levels of c-Myc (Myc) are reduced dramatically during late stage erythroid maturation, coinciding with cell cycle arrest in G1 phase and enucleation, suggesting possible roles for c-Myc in
Chemotherapeutics (e.g., aurora kinase inhibitors) designed to target proliferative cells are often nonspecific for tumor cells as normal cycling cells are also susceptible. Indeed, one of the major dose-limiting toxicities of aurora kinase inhibitors is a dangerous depletion of neutrophils in patients. In this study we proposed a strategy to selectively target p53 mutant cells while sparing norma
Geotechnical engineering is the science dealing with mechanics of soils and rocks and its engineering applications. Geotechnical engineering projects vary in a wide range, from evaluation of the stability of natural slopes and man-made soil deposits, to the design of earthworks and foundations. Traditional methods, using manual calculations or simplified computational methods, do not, as a rule, t
The two mitotic centrosomes direct spindle bipolarity to maintain euploidy. Centrosome amplification - the acquisition of ≥3 centrosomes - generates multipolar mitoses, aneuploidy, and chromosome instability to promote cancer biogenesis. While much evidence suggests that Cdk2 is the major conductor of the centrosome cycle and that it mediates centrosome amplification induced by various altered tum
Previously, the connection between cell proliferation and Wnt signaling focused on transcriptional activation of cyclin D1 and c-myc, which control the G1/S transition of the cell cycle. In this issue of Developmental Cell, the Niehrs group demonstrates mitotic activation of Wnt signaling by a novel Cdk/cyclin complex containing Cdk14 (PFTK1) and cyclin Y.
Cdk2 was once believed to play an essential role in cell cycle progression, but cdk2-/- mice have minimal phenotypic abnormalities. In this study, we examined the role of cdk2 in hepatocyte proliferation, centrosome duplication and survival. Cdk2-/- hepatocytes underwent mitosis and had normal centrosome content after mitogen stimulation. Unlike wild-type cells, cdk2-/- liver cells failed to under
Early studies on cell cycle regulation were based on experiments in model systems (Yeast, Xenopus, Starfish, Drosophila) and have shaped the way we understand many events that control the cell cycle. Although these model systems are of great value, the last decade was highlighted by studies done in human cells and using in vivo mouse models. Mouse models are irreplaceable tools for understanding t
After a decade of extensive work on gene knockout mouse models of cell-cycle regulators, the classical model of cell-cycle regulation was seriously challenged. Several unexpected compensatory mechanisms were uncovered among cyclins and Cdks in these studies. The most astonishing observation is that Cdk2 is dispensable for the regulation of the mitotic cell cycle with both Cdk4 and Cdk1 covering fo
Once it was believed that Cdk2 was the master regulator of S phase entry. Gene knockout mouse studies of cell cycle regulators revealed that Cdk2 is dispensable for S phase initiation and progression whereby Cdk1 can compensate for the loss of Cdk2. Nevertheless, recent evidence indicates that Cdk2 is involved in cell cycle independent functions such as DNA damage repair. Whether these properties
The loss of p53 induces spontaneous tumors in mice, and p53 mutations are found in approximately 50% of human tumors. These tumors are generally caused by a number of events, including genomic instability, checkpoint defects, mitotic defects, deregulation of transcriptional targets, impaired apoptosis, and G 1 deregulation or a combination of these effects. In order to determine the role of protei
