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

Oncogene. 2006 Jan 12;25(2):260-70. doi: 10.1038/sj.onc.1209050.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Cycle
  • Cell Proliferation*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Chromatography, Affinity
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism*
  • Electrophoresis, Gel, Two-Dimensional
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Histone Chaperones
  • Humans
  • Immunoprecipitation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Plasmids
  • Protein Binding
  • Protein Phosphatase 2
  • RNA / metabolism
  • RNA, Messenger
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA, Single-Stranded
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Histone Chaperones
  • Neoplasm Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • SET protein, human
  • Transcription Factors
  • hnRNP A2
  • RNA
  • Glutathione Transferase
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2