Abstract

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.The expression of Ebp1 was studied in mononuclear cells obtained from the peripheral blood of 54 patients with AML by Western blot. The effects of Ebp1 expression on Proliferating Cell Nuclear Antigen (PCNA) expression and cell proliferation was measured using Western Blot, 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.Ebp1 is highly expressed in acute myeloid 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 proliferating cell nuclear antigen (PCNA) protein by preventing its interaction with Mdm2, for which it is a substrate.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.

View details for DOI 10.1158/1078-0432.CCR-15-2282

View details for PubMedID 26813358