Endoreduplication has been suggested to contribute to the development of hypertrophy of smooth muscle cells (SMCs) in hypertension. However, endoreduplication in vascular SMCs and the underlying molecular mechanisms are not clear. Treatment of human SMCs with 10 microM 2-methoxyestradiol (2-ME) for 24 h induces accumulation of cells with > or =4N DNA content, and some polyploid/aneuploid cells ...

The p27 cyclin-dependent kinase inhibitor is a negative regulator of cell-cycle progression. In many human epithelial malignancies, decreased expression of p27 correlates with high grade, early recurrence, and poor prognosis. To evaluate the prognostic significance of p27 in hepatocellular carcinoma (HCC), we studied 54 HCCs along with corresponding nontumoral tissue. Immunohistochemistry (IHC)...

To take into account polarization effects, the linear interaction energy model with continuum electrostatic solvation (LIECE) is supplemented by the linear-scaling semiempirical quantum mechanical calculation of the intermolecular electrostatic energy (QMLIECE). QMLIECE and LIECE are compared on three enzymes belonging to different classes: the West Nile virus NS3 serine protease (WNV PR), the ...

In normal cells in which DNA has been damaged, p53 induces the expression of p21; p21, in turn, binds to cyclin-dependent kinase 2 (cdk2) and inhibits its function. Inhibition of cdk2 results in cell cycle arrest in G0-G1. Although p53 is transcriptionally active and induces p21 expression in neuroblastoma (NB) cells, the G0-G1 checkpoint is attenuated. Here we report that the mechanism that me...

We describe a cell-free system from HeLa cells that initiates DNA replication under cell cycle control. G1 but not G2 phase nuclei initiate replication when coincubated with S phase nuclei in cytosolic extracts from S phase but not from G1 or G2 phase HeLa cells. S phase nuclei or an S phase nuclear extract are required for the initiation of semiconservative DNA replication in G1 nuclei but not...

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in many human malignant tumors including cervical cancer. Human papillomavirus (HPV) oncoprotein E7 is the key transformation factor in cervical cancer. Our previous data showed a positive association of CIP2A and HPV-16E7 protein levels; however, how CIP2A is regulated by HPV-E7 and...

The bovine papillomavirus E2 protein can inhibit the proliferation of HT-3 cells, a p53-negative cervical carcinoma cell line containing integrated human papillomavirus type 30 DNA. Here, we analyzed HT-3 cells to explore the mechanism of p53-independent E2-mediated growth inhibition. Expression of the E2 protein repressed expression of the endogenous human papillomavirus type 30 E6/E7 genes. T...

Using immunodepletion of cyclin E and the inhibitor protein p21WAF/CIP1, we demonstrate that the cyclin E protein, in association with Cdk2, is required for the elongation phase of replication on single-stranded substrates. Although cyclin E/Cdk2 is likely to be the major target by which p21 inhibits the initiation of sperm DNA replication, p21 can inhibit single-stranded replication through a ...

Most transitions in the eukaryotic cell cycle are catalyzed by cyclin-dependent kinases (Cdks, CDKs), complexes formed between a member of the Cdk family of protein kinases and a regulatory cyclin subunit. CDKs are among the most highly regulated enzymes known: Their activities are controlled through multiple mechanisms that include cyclin association, positive and negative phosphorylation even...

The Evi-1 transcriptional repressor protein has two distinct zinc finger DNA binding domains designated ZF1 and ZF2 and is implicated in the progression of human and murine leukemias, in which it is abnormally expressed. In this report, we show that Evi-1-expressing Rat1 fibroblasts are anchorage independent, have an abbreviated G1 phase of the cell cycle, and have a reduced requirement for ser...