RGD Reference Report - Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA transcription and cell size. - Rat Genome Database

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Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA transcription and cell size.

Authors: Muller, C  Bremer, A  Schreiber, S  Eichwald, S  Calkhoven, CF 
Citation: Muller C, etal., EMBO J. 2010 Mar 3;29(5):897-909. doi: 10.1038/emboj.2009.404. Epub 2010 Jan 14.
RGD ID: 10047291
Pubmed: PMID:20075868   (View Abstract at PubMed)
PMCID: PMC2810377   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2009.404   (Journal Full-text)

The messenger RNA of the intronless CEBPA gene is translated into distinct protein isoforms through the usage of consecutive translation initiation sites. These translational isoforms have distinct functions in the regulation of differentiation and proliferation due to the presence of different N-terminal sequences. Here, we describe the function of an N-terminally extended protein isoform of CCAAT enhancer-binding protein alpha (C/EBPalpha) that is translated from an alternative non-AUG initiation codon. We show that a basic amino-acid motif within its N-terminus is required for nucleolar retention and for interaction with nucleophosmin (NPM). In the nucleoli, extended-C/EBPalpha occupies the ribosomal DNA (rDNA) promoter and associates with the Pol I-specific factors upstream-binding factor 1 (UBF-1) and SL1 to stimulate rRNA synthesis. Furthermore, during differentiation of HL-60 cells, endogenous expression of extended-C/EBPalpha is lost concomitantly with nucleolar C/EBPalpha immunostaining probably reflecting the reduced requirement for ribosome biogenesis in differentiated cells. Finally, overexpression of extended-C/EBPalpha induces an increase in cell size. Altogether, our results suggest that control of rRNA synthesis is a novel function of C/EBPalpha adding to its role as key regulator of cell growth and proliferation.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nucleolus located_inIDA 10047291PMID:20075868UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P0674810047291PMID:20075868UniProt 
protein binding enablesIPIUniProtKB:P1748010047291PMID:20075868UniProt 
protein binding enablesIPIUniProtKB:Q1557310047291PMID:20075868UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Cebpa  (CCAAT/enhancer binding protein alpha)


Additional Information