Estrogen receptor (ER) expression and Her-2 amplification define specific subsets of breast tumors for which specific therapies exist. The S-phase kinase-associated protein Skp2 is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. Using microarray analysis and immunohistochemistry, we determined that higher levels of Skp2 are present ...

The F-box protein SKP2 promotes the G1-S transition by targeting key regulators for proteasomal degradation via its capacity to function as the specificity factor for the SKP1 Cullin F-box SCF(SKP2) ubiquitin ligase. SKP2 is a labile protein, the levels of which oscillate in a cell cycle-dependent manner. SKP2 accumulation is often deregulated in cancer, which indicates that temporal control of...

PURPOSE We previously reported the p27 expression level to be an independent prognostic factor, and a high S-phase kinase-associated protein 2 (Skp2) expression level was significantly correlated with a poor prognosis in patients with gastric cancer. We herein examined the Skp2 expression in breast cancer and attempted to identify any associations between the Skp2 expression status and either t...

Reduced expression level of p27, a cyclin-dependent kinase inhibitor, is associated with high aggressiveness and poor prognosis of various malignant tumors, including gastric carcinoma. S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of substrate-recognition subunits of Skp1-Cullin-F-box ubiquitin-protein ligase complexes, is necessary for p27 ubiquitination and degrada...

PURPOSE The purpose of this study was to examine Skp2 expression in epithelial ovarian tumors and to identify the association of Skp2 expression levels with patient survival. EXPERIMENTAL DESIGN Skp2 protein expression was examined by immunohistochemistry in 134 epithelial ovarian tumors [20 adenomas, 23 low malignant potential (LMP) tumors, and 91 adenocarcinomas]. Results of immunostaining ...

The gene of SKP2, located on chromosome 5p13, plays a critical role in cell cycle progression, especially at the G(1)-S transition, putatively through its control of several cell cycle regulator proteins including p27(kip1), p21(cip1), p57(kip2), p130, cyclin E, and c-Myc. Previous studies in this laboratory revealed that gain of chromosome 5p was often seen in esophageal squamous cell carcinom...

BCR-ABL is proposed to impair cell cycle control by disabling p27, a tumor suppressor that inhibits cyclin-dependent kinases. We show that in cell lines p27 expression is inversely correlated with expression of SKP2, the F-box protein of SCF, the E3 ubiquitin ligase that promotes proteasomal degradation of p27. Inhibition of BCR-ABL kinase causes G1 arrest, downregulation of SKP2 and accumulati...

It is believed that Rb blocks G1-S transition by inhibiting expression of E2F regulated genes. Here, we report that the effects of E2F repression lag behind the onset of G1 cell cycle arrest in timed Rb reexpression experiments. In comparison, kinase inhibitor p27Kip1 protein accumulates with a faster kinetics. Conversely, Rb knockout leads to faster p27 degradation. Rb interacts with the N ter...

Previous studies have shown that the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) is targeted for degradation by an SCF(Skp2) ubiquitin ligase complex and that this process requires Cks1, a member of the highly conserved Suc1/Cks family of cell cycle regulatory proteins. All proteins of this family have Cdk-binding and anion-binding sites, but only mammalian Cks1 binds to Skp2 and promotes...

PURPOSE Although antiproliferative drugs have been used to prevent scarring after filtration surgery in patients with glaucoma, there are complications associated with their use. In the present study, the authors investigated whether small interfering RNA (siRNA)-mediated gene silencing of Skp2 can be used to increase p27(kip1) level and inhibit cell proliferation in rabbit Tenon's capsule fibr...