1714 Cell Cycle volume 10 issue 11 Over the past decades it has become increasingly clear that the DnA damage response (DDR) plays a crucial role in the prevention of cancer. Our DnA is extremely vulnerable to genotoxic stress. Genotoxic insults commonly arise from within as well as from without the organism. From within, genotoxic stress can be imposed by toxic byproducts of cellular metabolis...

Cell cycle control during spermatogenesis is a highly complex process owing to the control of the mitotic expansion of the spermatogonial cell population and following meiosis, induction of DNA breaks during meiosis and the high levels of physiological germ-cell apoptosis. We set out to study how E2F1, a key controller of cell cycle, apoptosis, and DNA damage responses, functions in the develop...

The loss of the retinoblastoma tumor suppressor gene (RB) is common in many human cancers, including prostate. We previously reported that engineered deletion of RB in prostate epithelial cells results in sustained cell growth in serum-free media, a predisposition to develop hyperplasia and dysplasia in prostate tissue recombinant grafts, and sensitization to hormonal carcinogenesis. Examining ...

The E2F1 transcription factor is a recognized regulator of the cell cycle as well as a potent mediator of DNA damage-induced apoptosis and the checkpoint response. Understanding the diverse and seemingly dichotomous functions of E2F1 activity has been the focus of extensive ongoing research. Although the E2F pathway is frequently deregulated in cancer, the contributions of E2F1 itself to tumori...

Chronic inflammation contributes to tumorigenesis. The retinoblastoma protein (pRb), in its hyperphosphorylated form, releases E2 promoter binding factor-1 (E2F1), which drives cell proliferation. Here, we show that pRb is hyperphosphorylated in both mouse and human colitis. In turn, pRb hyperphosphorylation is associated with release of E2F1 from pRb, resulting in the activation of E2F1 target...

LEF-1 and E2F are both transcription factors involved in cell proliferation, differentiation and apoptosis. The present study shows for the first time that LEF-1 associates with E2F1 and further beta-catenin independently activates the E2F-responsive reporter gene by attenuating the interaction between E2F1 and Histone deacetylase 1 (HDAC1), which indicates that LEF-1, except for its function i...

Tumor necrosis factor-alpha (TNF-alpha) is expressed locally in the vessel wall after angioplasty and induces growth arrest and apoptosis in endothelial cells (ECs), thereby delaying reendothelialization. Prior studies have shown that direct antagonism of TNF-alpha, using a systemically administered soluble receptor, can enhance endothelial recovery and reduce neointimal thickening. These studi...

Thymic negative selection is the process in which maturing thymocytes that express T-cell receptors recognizing self are eliminated by apoptotic cell death. The molecular mechanism by which this occurs is poorly understood. Notably, genes involved in cell death, even thymocyte death, such as Fas, Fas-ligand, p53, caspase-1, caspase-3, and caspase-9, and Bcl-2 have been found to not be required ...

The Rb/E2F pathway is deregulated in most human brain tumors, and the finding that loss of E2F1 reduced pituitary tumorigenesis in Rb mice suggests that loss of pRb induces brain tumors by activating E2F1. We therefore investigated the role of E2F1 in the development and maintenance of brain cancer using a transgenic mouse model engineered to express E2F1 specifically within glial cells (GFAP-t...

The cell cycle-regulatory transcription factor E2F1 induces apoptosis of postmitotic neurons in developmental and pathological situations. E2F1 transcriptionally activates many proapoptotic genes including the cyclin-dependent protein kinase cell division cycle 2 (Cdc2). Necdin is a potent mitotic suppressor expressed predominantly in postmitotic neurons and interacts with E2F1 to suppress E2F1...