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 ...

Low expression of p27(Kip1) is associated with disease progression and an unfavorable outcome in several malignancies including oral squamous cell carcinoma (SCC). In addition, p27(Kip1) protein is thought to be degraded by Skp2 (S-phase kinase-associated protein 2). The purpose of this study was to examine whether Skp2 expression can be a useful prognostic factor in oral SCC patients treated b...

Non-Hodgkin lymphoma (NHL) is a primary tumor arising in lymph nodes and lymphoid tissue. The incidence of NHL is increasing at an annual rate of 3%. The human Jun activation domain-binding protein 1/COP9 signalosome subunit 5 (Jab1/CSN5) is a negative regulator of the cell cycle inhibitor p27Kip1 and abnormal expression of Jab1 is correlated with reduced p27 expression and associated with adva...

BACKGROUND S-phase kinase-associated protein 2 (Skp2) is a member of mammalian F-box proteins. The purpose of this study is to clarify the prognostic significance of expression of Skp2 related to gender, estrogen receptor (ER) and progesterone receptor (PGR) in soft tissue sarcomas (STS). Skp2 has been demonstrated to display an oncogenic function since its overexpression has been observed in m...

Altered DAB2IP gene expression often detected in prostate cancer (PCa) is due to epigenetic silencing. In this study, we unveil a new mechanism leading to the loss of DAB2IP protein; an oncogenic S-phase kinase-associated protein-2 (Skp2) as E3 ubiquitin ligase plays a key regulator in DAB2IP degradation. In order to unveil the role of Skp2 in the turnover of DAB2IP protein, both prostate cell ...

Recent studies have suggested that Skp2, an SCF-type ubiquitin ligase, positively regulates cell cycle through degradation of p27, which is an inhibitor of cyclin-dependent kinase 2 (CDK2), which drives cells from the G1 to S phase of cell cycles. In the present study, we examined key regulatory proteins involved in serum starvation-induced cell cycle arrest in human ovarian cancer cells, SK-OV...

Protein kinase Ci (PKCi) is an atypical PKC isoform and participates in multiple aspects of the transformed phenotype in human cancer cells. We previously reported that frequent amplification and overexpression of PKCi were correlated with lymph node metastasis in primary esophageal squamous cell carcinomas (ESCC). In the present study, short interfering RNA–mediated silencing of PKCi revealed ...

PURPOSE The purpose of this study is to clarify the prognostic significance of expression of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas (STS). Optimised treatment of STS requires better identification of high risk patients who will benefit from adjuvant therapy. The prognostic significance of Jab1, p16, p21, p62, Ki67 and Skp2 in STS has not been sufficiently investigated. EXP...

PURPOSE A low expression level of cyclin-dependent kinase (Cdk) inhibitor p27 is associated with high aggressiveness and poor prognosis of various carcinomas. Human Cdk subunit 1 (Cks1), as well as S-phase kinase-associated protein 2 (Skp2), is an essential and specific factor in the p27 proteolysis by SCF(Skp2) ubiquitin ligase. The purpose of this study is to clarify the clinical significance...

Epigenetic silencing of secreted wingless-type (Wnt) antagonists through hypermethylation is associated with tobacco smoking and with invasive bladder cancer. The secreted Wnt inhibitory factor-1 (WIF1) has shown consistent growth-inhibitory effect on various cancer cell lines. Therefore, we assessed the mechanisms of action of WIF1 by either restoring WIF1 expression in invasive bladder cancer...