Heterogeneous nuclear ribonucleoprotein A2 is a SET-binding protein and a PP2A inhibitor

• Published in: Oncogene Vol. 25; no. 2; pp. 260 - 270
• Main Authors: VERA, J, JAUMOT, M, ESTANYOL, J. M, BRUN, S, AGELL, N, BACHS, O
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 12-01-2006; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Cell Cycle; Cell cycle, cell proliferation; Cell growth; Cell physiology; Cell Proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cells, Cultured; Cercopithecus aethiops; Chromatography; Chromatography, Affinity; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; COS Cells; DNA, Single-Stranded - genetics; DNA, Single-Stranded - metabolism; Electrophoresis, Gel, Two-Dimensional; Fundamental and applied biological sciences. Psychology; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - genetics; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - metabolism; Histone Chaperones; Humans; Immunoprecipitation; Kinases; Leukemia; Molecular and cellular biology; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phosphatase; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Plasmids; Protein Binding; Protein Phosphatase 2; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - metabolism; RNA - metabolism; RNA, Messenger; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transcription Factors - genetics; Transcription Factors - metabolism; Binding protein; Ribonucleoprotein; SET protein; Cell cycle; Inhibitor; PP2A; hnRNPA2; Carcinogenesis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1209050

The oncoprotein SET participates in a diversity of cellular functions including cell proliferation. Its role on cell cycle progression is likely mediated by inhibiting cyclin B-cdk1 and the protein phosphatase 2A (PP2A). On identifying new SET cellular partners, we found that SET interacts in vitro and in vivo with the heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2); a protein involved in various aspects of mRNA biogenesis. The SET-binding region of hnRNPA2 is the RNP1 sequence that belongs to the RNA-binding domain (RBD) of this protein. We also found that hnRNPA2 has much higher affinity for single-standed DNA than for SET. On analysing the effect of hnRNPA2 on PP2A inhibition by SET, we observed that hnRNPA2 cooperates with SET on PP2A inhibition. This is because we found that hnRNPA2 is also a PP2A inhibitor. HnRNPA2 interacts with PP2A by the RNP1 sequence; however, to inhibit PP2A activity, the complete RBD is needed. We also observed that overexpression of hnRNPA2 inhibits PP2A activity and stimulates cell proliferation. Interestingly, the overexpression of the complete RBD is sufficient to stimulate proliferation. As hnRNPA2 is overexpressed in a variety of human tumors, our results suggest that hnRNPA2 might participate in oncogenesis by stimulating cell proliferation.