The human T-lymphotropic virus type 1 (HTLV-1) Tax binds the anaphase promoting complex (APC) and activates it ahead of schedule. Here, we show that APC activation by Tax induces rapid senescence (tax-IRS) independently of p53 and pRB. In response to tax, cyclin A, cyclin B1, securin, and Skp2 becomes polyubiquitinated and degraded starting in S phase. This is followed by a surge in p21(CIP1/WA...

In general, pituitary tumors are benign with low mitotic activity. Premature senescence has been considered to be a significant mechanism underlying this uniquely benign pituitary tumor. The present study aims to compare the expression of the associated proteins involved in premature senescence pathways among normal, aging and pituitary adenoma cells. We successfully induced the aging pituitary...

Eukaryotic cell cycle transitions are driven by E3 ubiquitin ligases that catalyze the ubiquitylation and destruction of specific protein targets. For example, the anaphasepromoting complex/cyclosome (APC/C) promotes the exit from mitosis via destruction of securin and mitotic cyclins, whereas CRL1 allows entry into S phase by targeting the destruction of the cyclin-dependent kinase (CDK) inhib...

A photochemical route for the synthesis of some benzopyronospiropyrans from 2-furyl-3cycloalkenyloxybenzopyrones involving H-abstraction is reported. How a methyl group on the furyl ring affects the product formation is also investigated. 1. Background Spiropyrans exhibit photochromism due to the photoequilibrium with their open chain analogues merocyanins – a property that makes them a materia...

When cells enter mitosis, the anaphase-promoting complex/cyclosome (APC/C) is activated by phosphorylation and binding of Cdc20. The RXXL destruction box (D-box) of cyclin B1 only binds Cdc20 after release of the spindle checkpoint in metaphase, initiating cyclin B1 ubiquitination upon chromosome bi-orientation. However, we found that cyclin B1, through Cdk1 and Cks, is targeted to the phosphor...

Human pituitary tumor transforming gene (PTTG) overexpression correlates with metastasis in multiple tumors, and yet its molecular mechanisms of action remain elusive. We detected PTTG overexpression in 66% (111 of 169) of primary esophageal squamous cell carcinoma (ESCC) tumor tissues by in situ hybridization. PTTG overexpression correlated with lymph node metastasis (P < 0.05). Ectopic PTTG o...

Pituitary tumor transforming gene (PTTG), the human ortholog of securin, is an oncogene. Few normal tissues express PTTG, although in the testis, it is more abundantly expressed. In cancer, however, its wide expression has been directly correlated with the proliferation and angiogenesis, although very little is known about the overall regulation of the PTTG gene. In this study, we investigate t...

The calcium-sensing receptor (CaR) is a seven transmembrane receptor incorporated into the cell membrane that is sensitive to extracellular calcium and other cations. The finding that the CaR is expressed on cancer cells has opened the door to a new understanding of the role of extracellular calcium as a promalignant stimulus through the CaR and its signaling apparatus as demonstrated in this t...

The Spindle Assembly Checkpoint (SAC) delays the onset of anaphase until every chromosome is properly bioriented at the spindle equator. Mutations in SAC genes have been found in tumors and compromised SAC function can increase the incidence of some carcinomas in mice, providing further links between cancer etiology, chromosome segregation defects and aneuploidy. Here we review recent developme...