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The tumor suppressor p27(Kip1) is an inhibitor of cyclin/cyclin-dependent kinase (CDK) complexes and plays a crucial role in cell cycle regulation. However, p27(Kip1) also has cell cycle-independent functions. Indeed, we find that p27(Kip1) regulates cell migration, as p27(Kip1)-null fibroblasts exhibit a dramatic decrease in motility compared with(More)
The generation of new neurons in the cerebral cortex requires that progenitor cells leave the cell cycle and activate specific programs of differentiation and migration. Genetic studies have identified some of the molecules controlling these cellular events, but how the different aspects of neurogenesis are integrated into a coherent developmental program(More)
In utero or early-life vitamin D deficiency is associated with skeletal problems, type 1 diabetes, and schizophrenia, but the prevalence of vitamin D deficiency in U.S. pregnant women is unexplored. We sought to assess vitamin D status of pregnant women and their neonates residing in Pittsburgh by race and season. Serum 25-hydroxyvitamin D (25(OH)D) was(More)
[1] We present a factor analysis-based method for differentiating air masses on the basis of source influence and apply the method to a broad suite of trace gas and aerosol measurements collected at Chebogue Point, Nova Scotia, during the summer of 2004 to characterize the chemical composition of atmospheric outflow from eastern North America. CO, ozone,(More)
In mammals there are two known groups of CDK-inhibitors of the cyclin D–CDK4/CDK6 kinases (Xiong et defined by a conserved amino-terminal domain that is Seattle, Washington 98104 sufficient for both stable binding to cyclin–CDK com-‡ Department of Pathology plexes and inhibition of CDK protein kinase activity. The Harvard Medical School Kip/Cip proteins can(More)
Entry into, progression through, and exit from the G1 phase of the mammalian cell cycle in response to extracellular mitogenic cues are presumed to be governed by cyclin-dependent kinases (Cdks) regulated by the D-type and E-type cyclins. Studies performed over more than a decade have supported the view that these holoenzymes are important, if not required,(More)
Arterial smooth muscle cells (SMCs) are arrested in the G1 phase of the cell cycle on polymerized type I collagen fibrils, while monomer collagen supports SMC proliferation. Cyclin E-associated kinase and cyclin-dependent kinase 2 (cdk2) phosphorylation are inhibited on polymerized collagen, and levels of the cdk2 inhibitors p27Kip1 and p21Cip1/Waf1 are(More)
BACKGROUND In many vertebrate cell lineages, precursor cells divide a limited number of times before they arrest and terminally differentiate into postmitotic cells. It is not known what causes them to stop dividing. We have been studying the 'stopping' mechanism in the proliferating precursor cells that give rise to oligodendrocytes, the cells that make(More)
SUMMARY Targeted disruption of the murine p27(Kip1) gene caused a gene dose-dependent increase in animal size without other gross morphologic abnormalities. All tissues were enlarged and contained more cells, although endocrine abnormalities were not evident. Thymic hyperplasia was associated with increased T lymphocyte proliferation, and T cells showed(More)
ences in substrate preference between CDK1 and CDK2 (Holmes and Solomon, 1996), and there is no compelling 1100 Fairview Avenue North Seattle, Washington 98104 evidence that CDK2 and CDK1 are intrinsically different with regard to their ability to initiate S and M phases. Indeed, when either of these genes are expressed in budding yeast they can rescue(More)