Cx43 And AKAP95 Regulate Cell G1-S Transition By Competitively Binding To Cyclin E

With the development of medical molecular biology in recent years,there have been reported that lung cancer is characterized by disorder of cell growth and proliferation.Abnormal cell proliferation,differentiation and apoptosis can lead to the occurrence and development of lung cancer,and the irregulation cell cycle may cause canceration.Therefore studying cancer in the respect of cell cycle has become a hot research,Cyclin E has been considered to be a oncogene in many studies,its high expression could induce G1 phase shortening,making cells crossed G1 phase and reached S phase directly,causing centrosome doubling,and leading to malignant proliferation and canceration of cells.Connexin 43,playing an important role in gap junction channel biological functions,could also regulate cell proliferation,development and malignant transformation.Overexpression of Cx43 could slow down cell growth and block cell cycle at G1/S,research showed that AKAP95 protein promotes cell proliferation by binding to cyclin E1 and cyclin E2,overexpression of AKAP95 could promote cell cycle progression,Cx43 and AKAP95 presented periodic expression,combination and separation in cell cycle process.The study focused on the relationship between Cx43,AKAP95 and cyclin E as well as their effect on cell cycle by overexpressing Cx43 and AKAP95 genes in A549 cells,and the binding quantities was detected.PDGF-BB was used to further verify the interrelation between these three kinds of protein.The experimental results proved that,1.Overexpression of Cx43 could inhibit cell proliferation,while overexpression of AKAP95 could promote cell proliferation.2.Overexpression of Cx43 might promote the degradation of cyclin E1,while Overexpression of AKAP95 might inhibit the degradation of.cyclin E.3.When Cx43 overexpressed,the combination of AKAP95 and cyclin E reduced,and the combination of Cx43 and AKAP95 increased,when AKAP95 overexpressed,the combination of AKAP95 and cyclin E increased,and the combination of Cx43 and cyclin E decreased as well as AKAP95 and Cx43.4.PDGF-BB treatment to Beas-2B cells could increased the expression of AKAP95 and cyclin E,and there was a competitive binding among AKAP95,Cx43 and Cyclin E.6.PKA might be involved in Cx43-AKAP95’s G1-S transition regulating.