Annexin A2 is a novel RNA-binding protein.
Annexin A2 (ANXA2) is a Ca(2+)-binding protein that is up-regulated in virally transformed cell lines and in human tumors. Here, we show that ANXA2 binds directly to both ribonucleotide homopolymers and human c-myc RNA. ANXA2 was shown to bind specifically to poly(G) with high affinity (K(d) = 60 nM) and not to poly(A), poly(C), or poly(U). The binding of ANXA2 to poly(G) required Ca(2+) (A(50%) = 10 microM). The presence of RNA in the immunoprecipitates of ANXA2 isolated from HeLa cells established that ANXA2 formed a ribonucleoprotein complex in vivo. Sucrose gradient analysis showed that ANXA2 associates with ribonucleoprotein complexes and not with polyribosomes. Reverse transcriptase-PCR identified c-myc mRNA as a component of the ribonucleoprotein complex formed by ANXA2 in vivo, and binding studies confirmed a direct interaction between ANXA2 and c-myc mRNA. Transfection of LNCaP cells with the ANXA2 gene resulted in the up-regulation of c-Myc protein. These findings identify ANXA2 as a Ca(2+)-dependent RNA-binding protein that interacts with the mRNA of the nuclear oncogene, c-myc.
Filipenko
Nolan R
NR
Cancer Biology Research Group, Departments of Biochemistry & Molecular Biology and Oncology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
MacLeod
Travis J
TJ
Yoon
Chang-Soon
CS
Waisman
David M
DM
D017306:Annexin A2 / Q000032:analysis* / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis* / Q000378:metabolism; D015854:Up-Regulation
C472822:ANXA2 protein, human; D017306:Annexin A2; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D012313:RNA