REGULATION OF CDC25A IN HUMAN TUMOR CELLS BY CYCLIN-DEPENDENT KINASE 2

摘要: Deregulation of normal cell cycle control is essential for malignant transformation. The Cdc25A dual-specificity phosphatase promotes progression by dephosphorylating and activating the cyclin-dependent kinases. has oncogenic anti-apoptotic activity overexpressed in many human tumors. mechanisms which cancer are unknown. protein levels downregulated checkpoints response to genotoxic stress; frequently compromised tumor cells. In addition, under physiologic conditions, half-life short. Alterations regulatory could be sufficient result overexpression this protein. While downregulation stress occurs through defined signal transduction pathways, regulation non-stressed cells poorly understood. purpose thesis was examine physiological goals our studies were: 1) investigate cells; 2) understand how Cdk2 kinase regulates levels; 3) explore mechanism turnover. results revealed that interphase regulated, part, activity, does not regulate turnover affecting several known pathways stability. Recent reports on role ubiquitin ligases have identified phosphorylation sites necessary efficient recruitment ligases. kinase(s) responsible phosphorylating these serine residues remain identified, although one prime candidate. initial interactions between focused an auto-amplification feedback loop increased catalytic both proteins, it now appears also stability plays important regulating during progression.