NOM1: Subcellular Localization and Interacting Proteins. Finding Clues to its Cellular Function

Abstract

NOM1, a nucleolar, eIF4A binding protein was recently discovered based on its location near the recurrent chromosome 7q36 breakpoint found in pediatric patients with acute myeloid leukemia that carry the 7q36;12p13 translocation. The predicted NOM1 protein contains two domains (MIF4G and MA3) that are also found in several proteins that function in translation, proliferation, transformation, and apoptosis. The nucleolar localization of NOM1 suggests that it is involved in processes occurring in the nucleolus including rDNA transcription, pre-rRNA processing and ribosome assembly. In this study we confirm that NOM1 localizes to the nucleolus through a basic region contained in its amino-terminal 240 amino acids. Based on heterokaryon data, NOM1 is likely to function in the nucleolus and nucleus as it does not shuttle to the cytoplasm. We also show by GST pull-downs that NOM1 interacts with several proteins found in the nucleolus including eIF4A3, NOLC1 (Nopp140), and the catalytic subunit of Protein Phosphatase 1 (PP1CA). Each of these proteins has been linked either directly or indirectly to the process of 40S ribosomal subunit biogenesis. This suggests a role for NOM1 in the ribosome biosynthesis pathway.