The generation of glutamatergic neurons by stem and progenitor cells is a complex process involving the tight coordination of multiple cellular activities, including cell cycle exit, initiation of neuronal differentiation and cell migration. The mechanisms that integrate these different events into a coherent program are not well understood. Here we show that the cyclin-dependent kinase inhibit...

p27kip1 is a cyclin-dependent kinase inhibitor that regulates progression from G1 into S phase. Aberrations in cell cycle control are often observed in tumors and might even be necessary in tumor development. Recent reports showed that low p27kip1 expression is associated with poor prognosis in several tumors and leukemia. To investigate the expression of p27kip1 in malignant lymphomas and eluc...

BACKGROUND The p27KIP1 gene, whose protein product is a negative regulator of the cell cycle, is a potential tumor suppressor gene; however, no tumor-specific mutations of this gene have been found in humans. This study was undertaken to identify and to assess potential alterations of p27KIP1 gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer. ...

cellular and molecular pathways link thrombosis and innate immune system during sepsis. extrinsic pathway activation of protease thrombin through fviia and tissue factor (tf) in sepsis help activate its endothelial cell (ec) membrane protease activated receptor 1 (par-1). thrombin adjusts the ec cycle through activation of g proteins (g12/13), and later through rho gefs (guanine nucleotide exch...

Arterial lesions in cardiovascular diseases are characterized by proliferation and migration of smooth muscle cells as well as deposition of connective tissue matrix. Factors that stimulate vascular smooth muscle cell (VSMC) proliferation are well described; however, the role of proteins that limit intimal hyperplasia is not well understood. To examine the function of Kip/Cip and INK cyclin-dep...

Cks1 plays an essential role in SCFSkp2-mediated ubiquitination, and consequently turnover, of the cdk2 inhibitor and tumor supressor p27Kip1. High Cks1 expression is associated with aggressive breast tumors and correlates with low p27Kip1 levels in some cases, although it is also an independent prognostic marker for survival, and provides predictive information in addition to that provided by ...

Regulation of the cell cycle is essential for carcinogenesis. The cell cycle is controlled by cyclin-dependent kinases (CDKs), which are upregulated by cyclins and downregulated by CDK inhibitors (CDKIs). Decreased p27Kip1 expression has been associated with survival rate, tumor size, histological differentiation and the presence of lymph node metastasis in patients with various types of cancer...

While it is well established that PPARgamma ligands inhibit cell growth and induce apoptosis in colon cancer cells, the mechanism of these effects of PPARgamma ligands is unclear. In this report, we demonstrate that the PPARgamma ligand, ciglitazone, exhibits an anti-proliferative effect and blocks G1/S cell cycle progression through regulation of p27kip1 protein levels and inhibition of Cdk2 a...

We show that treatment of a panel of thyroid carcinoma cell lines naturally harboring the RET/PTC1 oncogene, with the RET kinase inhibitors PP1 and ZD6474, results in reversible G1 arrest. This is accompanied by interruption of Shc and mitogen-activated protein kinase (MAPK) phosphorylation, reduced levels of G1 cyclins, and increased levels of the cyclin-dependent kinase inhibitor p27Kip1 beca...

MicroRNAs (miRNAs) regulate tumorigenesis by inhibiting gene expression. In this study, we showed that miR-320a expression is decreased in human gastric cancer tissues and correlates inversely with expression of FoxM1, a key cell cycle regulator involved in gastric carcinoma. By contrast, the expression of P27KIP1, a downstream effector of FoxM1, correlates positively with miR-320a levels. Luci...