Role of Phosphorylation in the Regulation of p27 Function of Breast Cancer

摘要

Ring-finger proteins serve many vital functions within the cell. We have identified RNF11, a novel 154 amino acid ring-finger containing protein, which is elevated in breast cancer. It is unclear as to whether RNF11 is regulated transcriptionally or translationally. Within its ring-finger domain, RNF11 contains an AKT phosphorylation site (T135) that is situated within a 14- 3-3 binding domain. RNFll binds 14-3-3 and this binding is regulated by AKT phosphorylation of RNF11 at T135. AKT phosphorylation of RNFll appears to alter RNF11 subcellular localization and accelerate the degradation of cytoplasmic RNF11. These findings may be important in breast cancer, where active AKT is associated with poor prognosis. Disregulation of proper RNF11 function by AKT may prove to be detrimental to patient outcomes making RNF11 a potential target for novel cancer therapeutics.