Phosphorylation And Function Of RanBP3L

Cancer,cardiovascular disorder and neurologic disease are the principal factors that threat human health.Research on cancer is the hot point of biomedical filed.Both of chemical and genetic agents lead to the birth and development of cancer.The chemical agents include radiation,UV,toxicant,smoking and alcohol,meanwhile,the genetic include DNA mutation,chromatin abnormality,and anomalous activity of proto-oncogenes.In early,tumor cells are benign,and as grow,they metastasize to other organs beside or far,forming new metastasis foci,threating man's health.Before metastasis,a couple of epithelial tumor cells transformed into mesenchymal-like cells to get rid of the limit of the extracellular matrix and go to blood and lymph liquid by crossing over the blood capillary.Most of them are killed by immune cells,and only a few survive,establishing new metastasis foci by transforming into epithelial cells again.Epithelial-mesenchymal transition and Mesenchymal-epithelial transition are of great importance in cancer process.As known,EMT plays a role in the development of cancer.During EMT,the epithelial cells require mesenchymal markers and lose the epithelial markers.The shapes become spindle-like,the co-junctions are reduced and the polarity is lost.The epithelial markers like E-cadherin,?-catenin,Occludin decrease,on the opposite,the mesenchymal markers like N-cadherin,Vimentin,Fibronectin increase.Research over the past shows transcriptional factors like Snail,Slug,Twist,zinc-finger proteins are main drivers of EMT progress.RanBP3L plays a negative role by transporting smadl/5/8 out of nucleus in BMP signaling.To further study the function of RanBP3L,we looked into the similar protein RanBP3 and found the Akt-recognizing sequence RXRXXS/T is shared by both,by comparing the structure and sequence of RanBP3L and RanBP3.Our research uncovers that Serine 77 on RanBP3L could be phosphorylated by Akt and dephosphorylated by PPM1A,and the cells show mesenchymal-like characters when they express RanBP3L stably.The function of promoting EMT by RanBP3L is related with phosphorylation of Serine 77.In conclusion,Our research discovers the kinase and phosphatase of RanBP3L,and a new role of promoting EMT of RanBP3L.