Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes.
Fiche publication
Date publication
août 2014
Journal
Leukemia
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen, Pr GIRODON François, Dr JEGO Gaëtan, Dr BELLAYE Pierre-Simon, Pr BONNIAUD Philippe, Dr DUPLOMB-JEGO Laurence
Tous les auteurs :
Jego G, Lanneau D, De Thonel A, Berthenet K, Hazoumé A, Droin N, Hamman A, Girodon F, Bellaye PS, Wettstein G, Jacquel A, Duplomb L, Le Mouël A, Papanayotou C, Christians E, Bonniaud P, Lallemand-Mezger V, Solary E, Garrido C
Lien Pubmed
Résumé
In addition to their cytoprotective role in stressful conditions, heat shock proteins (HSPs) are involved in specific differentiation pathways, for example, we have identified a role for HSP90 in macrophage differentiation of human peripheral blood monocytes that are exposed to macrophage colony-stimulating factor (M-CSF). Here, we show that deletion of the main transcription factor involved in heat shock gene regulation, heat shock factor 1 (HSF1), affects M-CSF-driven differentiation of mouse bone marrow cells. HSF1 transiently accumulates in the nucleus of human monocytes undergoing macrophage differentiation, including M-CSF-treated peripheral blood monocytes and phorbol ester-treated THP1 cells. We demonstrate that HSF1 has a dual effect on SPI1/PU.1, a transcription factor essential for macrophage differentiation and whose deregulation can lead to the development of leukemias and lymphomas. Firstly, HSF1 regulates SPI1/PU.1 gene expression through its binding to a heat shock element within the intron 2 of this gene. Furthermore, downregulation or inhibition of HSF1 impaired both SPI1/PU.1-targeted gene transcription and macrophage differentiation. Secondly, HSF1 induces the expression of HSP70 that interacts with SPI1/PU.1 to protect the transcription factor from proteasomal degradation. Taken together, HSF1 appears as a fine-tuning regulator of SPI1/PU.1 expression at the transcriptional and post-translational levels during macrophage differentiation of monocytes.
Mots clés
Animals, Antigens, CD, analysis, Antigens, Differentiation, Myelomonocytic, analysis, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, physiology, Gene Expression Regulation, Humans, Macrophages, cytology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Monocytes, cytology, Proteasome Endopeptidase Complex, metabolism, Proto-Oncogene Proteins, genetics, Receptors, Cell Surface, analysis, Trans-Activators, genetics, Transcription Factors, physiology
Référence
Leukemia. 2014 Aug;28(8):1676-86