Substantial evidence supports the oncogenic role of the E3 ubiquitin ligase S-phase kinase-associated protein 2 (Skp2) in many types of cancers through its ability to target a broad range of signaling effectors for ubiquitination. Thus, this oncogenic E3 ligase represents an important target for cancer drug discovery. In this study, we report a novel mechanism by which CG-12, a novel energy res...

We have previously demonstrated the inverse correlation of Jab1 and p27 proteins, as well as prognostic significance in epithelial ovarian carcinomas. In order to investigate Skp2 protein and its correlation with Jab1, p27, and clinical outcome, we evaluated Skp2 expression in a group of epithelial ovarian tumors. Immunohistochemical analysis was performed on 80 cases of ovarian tumors (33 beni...

Colon cancer is a common type of malignancy in the digestive system. The aim of the present study was to investigate the role of S-phase kinase-associated protein 2 (Skp2) in colon carcinoma and to identify whether depletion of Skp2 by Skp2‑RNA interference (RNAi) attenuates the proliferation and migration of colon carcinoma. Three pairs of small interfering (si)RNA were designed based on the S...

Skp2 E3 ligase is overexpressed in numerous human cancers and plays a critical role in cell-cycle progression, senescence, metabolism, cancer progression, and metastasis. In the present study, we identified a specific Skp2 inhibitor using high-throughput in silico screening of large and diverse chemical libraries. This Skp2 inhibitor selectively suppresses Skp2 E3 ligase activity, but not activ...

BACKGROUND S-phase kinase protein 2 (Skp2), an F-box protein, targets cell cycle regulators via ubiquitin-mediated degradation. Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival. In melanoma, however, the prognostic significance of subcellular Skp2 expression remains controversial. METHODS To investigate the role of Skp2 in melanoma development, we ...

E3 ubiquitin ligase Skp2 attaches ubiquitin to its target proteins and marks them for destruction by the 26S proteasome. This mechanism participates in a number of important cellular processes such as cell proliferation, DNA replication, V(D)J recombination, gene transcription, cellular metabolism and senescence. Skp2 is oncogenic. It is overexpressed in various solid tumors and hematological m...

Hepatitis B X-interacting protein (HBXIP) is a novel oncoprotein. We have previously reported that HBXIP promotes the proliferation and migration of breast cancer cells. S-phase kinase-associated protein 2 (Skp2) is another oncoprotein which is important for migration. In this study, we investigated whether Skp2 is involved in the migration enhanced by HBXIP in ovarian cancer. The expression of...

Cell adhesion is essential for cell cycle progression in most normal cells. Loss of adhesion dependence is a hallmark of cellular transformation. The F-box protein Skp2 (S-phase kinase-associated protein 2) controls G(1)-S-phase progression and is subject to adhesion-dependent transcriptional regulation, although the mechanisms are poorly understood. We identify two cross-species conserved bind...

PURPOSE The purpose is to investigate the clinical relevance of altered patterns of p27 and Skp2 expression in African-American patients with localized prostate cancer. The abundance of p27, an inhibitor of cell proliferation, is controlled by Skp2-dependent proteolysis. EXPERIMENTAL DESIGN A well-characterized cohort of 162 African-Americans who underwent radical prostatectomy at the Veteran...

PURPOSE Improper proliferation of lens epithelial cells is causally related to posterior capsule opacification. In the present study, we investigated whether small interfering RNA (siRNA)-mediated gene silencing of S-phase kinase-interacting protein 2 (Skp2) can be employed to inhibit rabbit lens epithelial cell (rLEC) proliferation by increasing the p27(kip1) level. METHODS A plasmid contain...