Over‐expression of Aurora‐A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1

Publisher Website
Google Scholar
Abstract
Aurora‐A is a centrosomal serine‐threonine kinase that regulates mitosis. Over‐expression of Aurora‐A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora‐A over‐expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over‐expressed Aurora‐A is not restricted to the centrosomes but is also found in the cytoplasm. This over‐expressed Aurora‐A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora‐A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over‐expressed Aurora‐A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h‐CPEB. In vitro experiments revealed that Aurora‐A binds directly to, and phosphorylates, h‐CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora‐A and h‐CPEB were over‐expressed, and they were further promoted in the presence of an Aurora‐A activator Ajuba. Our results suggest a function of ectopically over‐expressed Aurora‐A that might be relevant for carcinogenesis.