User:Iris To/Retinoblastoma Protein Regulation: Difference between revisions

From previous studies, it has been determined that the phosphorylation state and activity of Rb are controlled by a balance of kinase and phosphatase activity, in which Cdks phosphorylate Rb from late G1 to mitosis and the enzyme protein phosphatase 1 (PP1c) dephosphorylates Rb for mitotic exit<ref name=Hirschi>PMID: 20694007</ref>.  An enzyme-docking site for PP1c was determined to overlap with the docking site for Cdks, more specifically the RxL Cyclin binding site<ref name=Lowe>PMID:12501191</ref> that brings Cdk-Cyclins to Rb, through a crystal structure; this crystal structure initiated studies on phosphatase and kinase competition for the docking site. It has been found that PP1c directly inhibits phosphorylation of RbC from Cdk2-CycA, which is not affected by phosphatase activity but by the presence of the KLRF docking site, which binds PP1c to a specific site of Rb<ref name=Hirschi>PMID: 20694007</ref>.  In addition, it has been observed that PP1c makes complexes with RbC when there are many phosphatases produced, thus overthrowing Cdk activity and inhibiting cell progression from the G1 phase.  This competition is important in terms of cell signaling, which is affected by response to cellular stress, cell cycle exit, DNA damage, etc<ref name=Hirschi>PMID: 20694007</ref>.  Studies determined a biochemical mechanism where directly competing kinases and phosphatase activity regulates Rb phosphorylation and activity, but there has not been an established study that defined a mechanism that controlled the outcome of the competition between each enzyme<ref name=Hirschi>PMID: 20694007</ref>.