Cyclin A2 plays a key role in cell cycle regulation. It is essential in embryonic cells and in the hematopoietic lineage yet dispensable in fibroblasts. In this paper, we demonstrate that Cyclin A2-depleted cells display a cortical distribution of actin filaments and increased migration. These defects are rescued by restoration of wild-type Cyclin A2, which directly interacts with RhoA, or by a...

Cyclin E1 regulates the initiation of S-phase in cellular division. However, in many cancers, cyclin E1 is aberrantly overexpressed and this molecular phenotype correlates with increased tumor aggressiveness and poor patient survival. The molecular cause(s) of cyclin E1 abnormalities in cancers is poorly understood. Here, we show that cyclin E1 overexpression in cancer is promoted by dysregulat...

There is remarkable redundancy between the Cyclin-Cdk complexes that comprise the cell cycle machinery. None of the mammalian A-, D-, or E-type cyclins are required in development until implantation, and only Cdk1 is essential for early cell divisions. Cyclin B1 is essential for development, but whether it is required for cell division is contentious. Here, we used a novel imaging approach to a...

A total of two major isoforms, cyclin D1a and cyclin D1b, are generated from the human cyclin D1 gene by alternative splicing. Cyclin D1b is scarcely expressed in normal tissues; however, it is expressed at a high frequency in certain types of cancerous tissue. The present authors previously constructed cyclin D1b transgenic (Tg) mice and identified rectal tumors, including adenocarcinoma and s...

Using an in vitro chromatin assembly assay in Xenopus egg extract, we show that cyclin E binds specifically and saturably to chromatin in three phases. In the first phase, the origin recognition complex and Cdc6 prereplication proteins, but not the minichromosome maintenance complex, are necessary and biochemically sufficient for ATP-dependent binding of cyclin E--Cdk2 to DNA. We find that cycl...

D- and E-type cyclins mediate G(1)-S phase cell cycle progression through activation of specific cyclin-dependent kinases (cdk) that phosphorylate the retinoblastoma protein (pRb), thereby alleviating repression of E2F-DP transactivation of S-phase genes. Cyclin D1 is often overexpressed in a variety of cancers and is associated with tumorigenesis and metastasis. Loss of cyclin D can cause G(1)...

Abstract. Hyperplasia of mesangial cells (MC) is a frequent finding in glomerulonephritis. The control and function of cyclin D1, a regulator of cell cycle progression, in MC proliferation in vivo and in vitro were investigated. In a rat model of mesangioproliferative glomerulonephritis, increases in the number of cyclin D1-positive MC nuclei were prominent on day 5 of the disease, preceding th...

Cyclin D1 plays an essential regulatory role in the G1 phase of the cell cycle. The cyclin D1 gene is amplified in 20–50% of squamous cell carcinomas (SCCs), and the protein is overexpressed in up to 80% of SCCs. Our hypothesis was that gene transduction of antisense (AS) cyclin D1 in human SCCs in vivo would result in tumor reduction. A cyclin D1 cDNA was inserted into an E1/E3-deficient serot...