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

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. Ó2016 AACR.

Comprehensive in vivo identification of the c-Myc mRNA protein interactome using HyPR-MS

“…TRAP1 promotes IRESdependent translation and attenuates cap-mediated translation; down-regulation of TRAP1 has been associated with lower c-Myc protein levels (Matassa et al 2014), suggesting it regulates IRES-dependent c-Myc translation. Finally, EBP1 is known to interact with IRES of the footand-mouth disease virus, and its expression in K562 is functionally related with cell proliferation, acting on rRNA synthesis and proliferating cell nuclear antigen levels (Monie et al 2007;Nguyen le et al 2016). Our finding by HyPR-MS that EBP1 binds c-Myc mRNA suggests EBP1 could promote K562 cell proliferation by regulating c-Myc mRNA expression and specifically its translation initiation.…”

Distinct Interactions of EBP1 Isoforms with FBXW7 Elicits Different Functions in Cancer

“…EBP1 was originally identified as an ErbB3 binding protein which was considered as an oncogene or tumor suppressor in different circumstances (38–41) and has prognostic significance in a panel of cancers such as cervical (7, 42), pancreatic (6), hepatocellular (43), brain (44) and other tumors. Recent study has clarified that EBP1 possesses two isoforms, the longer form P48 and the shorter form P42, which distinctively regulate cell survival and differentiation (5).…”

Systematic Screen forDrosophilaTranscriptional Regulators Phosphorylated in Response to Insulin/mTOR Pathway

“…Interestingly, we demonstrated here that dPA2G4 is under similar dual regulation by phosphorylation and gene expression. In mammalian cells, PA2G4 has been found to localize to the nucleolus, bind to Pol I, and promote rRNA expression ( Karlsson et al 2016 ; Nguyen et al 2016 ). It can be therefore hypothesized that PA2G4 is a candidate to cooperate with PWP1 in regulating nutrient-responsive ribosome biogenesis in vivo .…”