Expression and Role of the ErbB3-Binding Protein 1 in Acute Myelogenous Leukemic Cells

Clin Cancer Res. 2016 Jul 1;22(13):3320-7. doi: 10.1158/1078-0432.CCR-15-2282. Epub 2016 Jan 26.

Abstract

Purpose: The ErbB3-binding protein 1 (Ebp1) has been implicated in diverse cancers as having either oncogenic or tumor suppressor activities. The present study was undertaken to determine the effects of Ebp1 expression in AML cells and to determine the mechanisms by which Ebp1 promotes cell proliferation in these cells.

Experimental design: The expression of Ebp1 was studied in mononuclear cells obtained from the peripheral blood of 54 patients with AML by Western blot analysis. The effects of Ebp1 expression on proliferating cell nuclear antigen (PCNA) expression and cell proliferation was measured using Western blot analysis, immunoprecipitation, in vitro ubiquitination, and colony-forming assays. The role of Ebp1 in promoting rRNA synthesis and cell proliferation was evaluated by measuring the level of pre-rRNA and the recruitment of Pol I to rDNA.

Results: Ebp1 is highly expressed in acute myelogenous leukemia (AML) cells and regulates the level of ribosomal RNA (rRNA) synthesis by binding to RNA Polymerase I (Pol I) and enhancing the formation of the Pol I initiation complex. Ebp1 also increases the stability of PCNA protein by preventing its interaction with Mdm2, for which it is a substrate.

Conclusions: These results demonstrate an important role of Ebp1 in promoting cell proliferation in AML cells through the regulation of both rRNA synthesis and PCNA expression. Clin Cancer Res; 22(13); 3320-7. ©2016 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Proliferation
  • Humans
  • Leukemia, Myeloid, Acute / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Proliferating Cell Nuclear Antigen / biosynthesis*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • RNA Interference
  • RNA, Ribosomal / biosynthesis*
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Receptor, ErbB-3 / metabolism*
  • Tumor Cells, Cultured
  • Ubiquitination

Substances

  • Adaptor Proteins, Signal Transducing
  • PA2G4 protein, human
  • Proliferating Cell Nuclear Antigen
  • RNA, Ribosomal
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • ERBB3 protein, human
  • Receptor, ErbB-3