Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes
Abstract
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.
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FBW7 targets positive transcriptional regulators of PU.1 such as HSF1.
“While earlier studies reported that FBW7 targeted some of the positive transcriptional regulators of PU.1 such as HSF1 (53), GSK3 by phosphorylating PU.1 within its potential CPDs may instigate its recognition by FBW7 for subsequent ubiquitinmediated degradation indicating that FBW7 is a potent negative regulator of macrophage differentiation.”
From FBW7 Inhibits Myeloid Differentiation in Acute Myeloid Leukemia via GSK3-Dependent Ubiquitination of PU.1 (2021) · cites this paper as [53]
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- Authors
- Jego, G., Lanneau, D., De Thonel, A., Berthenet, K., Hazoumé, A., Droin, N., Hamman, A., Girodon, F., Bellaye, P.-S., Wettstein, G., Jacquel, A., Duplomb, L., Le Mouël, A., Papanayotou, C., Christians, E., Bonniaud, P., Lallemand-Mezger, V, Solary, E., & Garrido, C.
- Affiliations
- Inserm (FR)
- Université de Bourgogne (FR)
- Sorbonne Paris Cité (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Garrido, C
- ORCID
- Venue
- Leukemia
- Published
- 2014-02-07
- Volume
- 28
- Issue
- 8
- Pages
- 1676-1686
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- OpenAlex
- W2029019156
- Cited by
- 42
- References
- 37
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 1
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-LABX-0021)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- heat shock factor 1, macrophage differentiation, monocytes, macrophage colony-stimulating factor, HSP70, heat shock element, transcriptional regulation, post-translational regulation, proteasomal degradation, HSP90, THP-1 cells, bone marrow-derived macrophages
- MeSH terms
- Heat Shock Transcription Factors, CD163 Antigen, Proto-Oncogene Protein Spi-1, Animals, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Gene Expression Regulation, Humans, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Monocytes, Proto-Oncogene Proteins, Receptors, Cell Surface, Transcription Factors, Antigens, Differentiation, Myelomonocytic, Trans-Activators, Antigens, CD, Proteasome Endopeptidase Complex, Mice
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