The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.
EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.
Department of Medico-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Latina, Italy.
Donatella
D
Ponti
Institute of Genetics and Biophysics ABT, Via Pietro Castellino, Napoli, Italy.
Gian Carlo
GC
Bellenchi
Department of Medico-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Latina, Italy.
Rosa
R
Puca
Department of Medico-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Latina, Italy.
Daniela
D
Bastianelli
Department of Medico-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Latina, Italy.
Marella
M
Maroder
Department of Medico-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Latina, Italy.
Giuseppe
G
Ragona
RNA Biology, FRE 3402 CNRS-Universitè Pierre et Marie Curie, Paris, France.
Pascal
P
Roussel
Unit of Cell Biology, GIGA-Neuroscience, University of Liege, CHU SartTilman, Liege, Belgium.
Marc
M
Thiry
Department of Pathology and Laboratory Medicine, University of California, Irvine, California, United States of America.
Dan
D
Mercola
Department of Medico-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Latina, Italy.
Antonella
A
Calogero
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D051766:Early Growth Response Protein 1 / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012318:RNA Polymerase I / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics*; D012335:RNA, Ribosomal / Q000235:genetics*; D014158:Transcription, Genetic
D015415:Biomarkers; D051766:Early Growth Response Protein 1; D035463:Pol1 Transcription Initiation Complex Proteins; D012322:RNA Precursors; D012335:RNA, Ribosomal; C063844:transcription factor UBF; D012318:RNA Polymerase I