BACKGROUND/AIMS All-trans retinoic acid (ATRA), the active form of vitamin A, plays an important role in the growth arrest of numerous types of cancer cells. It has been indicated that cyclin-dependent kinase 5 (Cdk5) activity can be affected by ATRA treatment. Our previous results demonstrate the involvement of Cdk5 in the fate of prostate cancer cells. The purpose of this study is to examine ...

Advanced pulmonary arterial hypertension is characterized by extensive vascular remodeling that is usually resistant to vasodilator therapy. Mevastatin is an inhibitor of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase, the rate-limiting step for cholesterol synthesis. HMG-CoA reductase inhibitors have been shown to upregulate the cyclin-dependent kinase inhibitor p27 and to block cel...

p27 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G(1)/S progression, and whose activity is, in part, regulated through interactions with D-type cyclins. Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation resulting in deregulated cyclin D1. We previously showed that p27 expression in MCL, as assessed by immunohistochemistry (IHC), does no...

The use of natural compounds is promising in approaches to prevent and treat cancer. long-term application most currently employed chemotherapy techniques has toxic side effects. Eugenol, a phenolic phytochemical extracted from certain essential oils, an anti-cancer effect. modulation autophagy can promote either the survival or apoptosis cancer cells. Triple-negative (MDA-MB-231) HER2 positive...

How extracellular signals communicate with the cell cycle is poorly understood. In this issue, two papers address this problem by reporting phosphorylation of the cyclin-dependent kinase inhibitor p27Kip1 on a tyrosine residue by nonreceptor tyrosine kinases, which decreases p27 stability. This new mechanism could explain how cells enter the cell cycle from a quiescent state.

B cell receptor (BCR) engagement of murine WEHI 231 immature B lymphoma cells leads sequentially to a drop in NF-kappa B and c-Myc, and induction of the p27(Kip1) cyclin-dependent kinase inhibitor, which promotes growth arrest and apoptosis. BCR engagement was recently shown to induce a drop in phosphatidylinositol 3-kinase (PI3K)/Akt signaling, preceding the increase in p27. As induction of p2...

BACKGROUND The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G1-S transition by promoting degradation of the cyclin-dependent kinase inhibitor p27(kip1) (p27). Recent evidence has indicated an oncogenic role of Skp2 in not only carcinogenesis but also lymphomagenesis. MATERIALS AND METHODS Clinicopathologic features and immunohistochemical expression of Skp...

Oncosuppressor miRNAs inhibit cancer cell proliferation by targeting key components of the cell cycle machinery. In our recent report we showed that miR-340 is a novel tumor suppressor in non-small cell lung cancer. miR-340 inhibits neoplastic cell proliferation and induces p27(KIP1) by targeting multiple translational and post-translational regulators of this cyclin-dependent kinase inhibitor.

Low or absent expression of the cyclin-dependent kinase inhibitor p27 serves as an excellent malignant marker for prostate and other human cancers. The level of p27 is regulated primarily by the ubiquitin E3 ligase SCF through ubiquitin-dependent proteolysis. Expression of the F-box protein SKP2 is inversely correlated with p27 in many cancers. To determine the role of SCF in proliferation and ...

Our recent studies showed that Src family kinases (SFKs) are important mediators of proliferation in renal proximal tubular cells (RPTC). In this study, we elucidate the signaling mechanisms that mediate SFK regulation of cell proliferation and cycle protein expression, and identify the SFK member responsible for these responses in a mouse RPTC line. Akt, a target of phosphoinositide-3-kinase (...