Relationship Between Abnormal Expression Of Skp2 And Clinical Significance Of Esophageal Carcinoma

A lot of studies in recent years have revealed that uncontrolled cell cycle plays an important role in cell over-proliferation, which ultimately results in cell carcinogenesis. The regulation of cell-cycle and cell proliferation is decided by the phase change of cell-cycle regulatory proteins, while the abundance of cell-regulatory proteins is decided by the expression of related genes and proteins degradation. It is well known that the proliferation and progression of cancer cells are closely related to abnormalities of various positive and negative cell cycle regulators, so studying these proteins is important to understand the mechanism of the proliferation and progression for cancer cells. It is well accepted that cell cycle in eukaryotic cells is controlled by various complexes composed of cyclin and cyclin dependent kinase (CDK). Protein degradation by the ubiquitin-proteasome pathway plays a fundamental part in the regulation of the eukaryotic cell cycle. Proteolysis of many G1 regulatory proteins is mediated by SCF ubiquitin ligases. SCF ubiquitin ligases are consist of Skp1, Cul1, Rbx1/Roc1, and one of many F-box proteins (Fbps). Skp2 is an Fbp, which targets many ubiquitin-mediated degradation of G1-and S-phase regulators. p27 and p21, which are CDK inhibitors and play an important role in negative regulation of the cell-cycle during G0 and G1 phases, are specifically recognized by Skp2 and then are targeted ubiquitination. Skp2 mediates the ubiquitylation of CKI p27 and p21, through which Skp2 plays an important role in cell-cycle and cell proliferation. Nowadays Skp2 is thought to be an oncogene. As a novel protein identified by human, cyclin dependent kinase inhibitor (CKI) could combine with cyclin-CDK complexes and inhibit the activity of those complexes. As a result, CKI arrests the transition from G1 phase to S phase in cell cycle and slowers the progression of cell proliferation suggesting that acts as anti-oncogene product. Now it is generally accepted that p21 and p27 are two broad-spectrum proteins in CKI family, which could block the cell cycle at G1 phase by preventing Rb protein from phosphorylation, so the abnormal expression of p21 and p27 is relevant to the initiation and...