NBA1 Interacts With PHGDH And Promotes Breast Cancer Growth

NBA1 is an important adaptor protein in breast cancer type 1 susceptibility protein(BRCA1)complex.It is vital to the structure of BRCA1 complex,as well as the protein stability of the other members in this complex.Functionally,it is involved in the assembling of DNA damage repair complex and required for DNA damage repair.To study novel functions of NBA 1,we performed protein interaction screening using NBA1 as a bait and found that PHGDH is an NBA1 interacting protein.PHGDH is the initial and rate-limiting enzyme of serine biosynthesis pathway(SSP),which branches from glycolysis.Moreover,PHGDH plays an important role in the onset and development of many types of breast cancers.In our study,we found that NBA and PHGDH have reciprocal interaction which is enhanced under glucose deprived condition.Moreover,the glycolytic intermediate 3-phosphoglycerate(3-PG)has a direct impact on the interaction of these two proteins.The domains required for interaction between NBA1 and PHGDH was also identified.Importantly,we found that NBA1 does not affect PHGDH tetramer formation but reduces its phosphorylation level by PKC?.Finally,we found that NBA1 promotes the growth of breast cancer cells by using cell and mice models.In all,we have conducted a preliminary assessment of the linkage between NBA1 and PHGDH,providing a potential mechanism of the regulation of tumor growth by NBA1 through its interaction with PHGDH,which could provide a new drug target to treat breast cancers.