NURIM Facilitates Cdc42 Activation Via Binding With Dbl Result In Non-small Lung Cancer Cell Migration

NURIM was first identified as a new type of inner nuclear membrane(INM)protein in a visual screen for nuclear envelope localizing proteins.NURIM(total length of 262 residues;29KD)is a six transmembrane domain protein with a hairpin turn in its C-terminal transmembrane domain,and both its N-and C-termini reside on the same side of the membrane.NURIM is different from the known nuclear envelope(NE)membrane proteins(such as LAP1,LBR et al.)as it is neither associated with nuclear pores nor with Lamins.Biochemical analysis showed that the protein is tightly bound to the INM.However,many aspects of NURIM are associated with human diseases and its biological functions remain largely unknown.Previous study has been shown that NURIM highly expressed in cancer cells and associated with higher tumor grade.Besides,it can inhibit the cell apoptosis and maintain the cell nuclear membrane forms.Cdc42(25KD)belongs to the Rho family of small GTPases,playing an important role in regulating the cytoskeleton reorganization,cell polarity,cell migration,cell malignant,transformation and so on.Besides,it participates in the progress of tumorigenesis,invasion and metastasis.Cdc42 with RhoGTP activity forms and RhoGDP inactivity forms.The conversion process is mainly regulated through guanine nucleotide exchange factor(GEF),catalytic GDP into GTP to activate Rho protein.Proto-oncogene Dbl(90KD)is one of the guanine nucleotide exchange factor(GEF)that modulates the activity of small G proteins,including the RhoGTPases family.In this study,we found that non-small cell lung cancer cell migration was inhibited,Cdc42 expression decreased and filopodia disappeared when NURIM was knocked down,through which we speculated that NURIM exerting function though RhoGTPases signaling pathway.In addition,we found that NURIM binds with Dbl further validated our hypothesis,but the exact machnism is still unclear.