Biology:SPI1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 gene.

Function

This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear protein binds to a purine-rich sequence known as the PU-box found on enhancers of target genes, and regulates their expression in coordination with other transcription factors and cofactors. The protein can also regulate alternative splicing of target genes. Multiple transcript variants encoding different isoforms have been found for this gene.

The PU.1 transcription factor is essential for hematopoiesis and cell fate decisions. PU.1 can physically interact with a variety of regulatory factors like TFIID, GATA-2, GATA-1 and c-Jun. The protein-protein interactions between these factors can regulate PU.1-dependent cell fate decisions. PU.1 can modulate the expression of 3000 genes in hematopoietic cells including cytokines. It is expressed in monocytes, granulocytes, B and NK cells but is absent in T cells, reticulocytes and megakaryocytes. Its transcription is regulated by various mechanisms .

PU.1 is an essential regulator of the pro-fibrotic system. In fibrotic conditions, PU.1 expression is perturbed in fibrotic diseases, resulting in upregulation of fibrosis-associated genes sets in fibroblasts. Disruption of PU.1 in fibrotic fibroblasts leads to them returning into their resting state from pro-fibrotic fibroblasts. PU.1 is seen to be highly expressed in extracellular matrix producing-fibrotic fibroblasts while it is downregulated in inflammatory/ ECM degrading and resting fibroblasts. The majority of the cells expressing PU.1 in fibrotic conditions remain to be fibroblasts with a few infiltrating lymphocytes. PU.1 induces the polarization of resting and inflammatory fibroblasts into fibrotic fibroblasts.

Structure

The ETS domain is the DNA-binding module of PU.1 and other ETS-family transcription factors.

Interactions

SPI1 has been shown to interact with:

• FUS,
• GATA2,
• IRF4, and
• NONO.

Further reading

• "The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene". Cell 61 (1): 113–124. April 1990. doi:10.1016/0092-8674(90)90219-5. PMID 2180582. 
• "Localization of the human oncogene SPI1 on chromosome 11, region p11.22". Human Genetics 84 (6): 542–546. May 1990. doi:10.1007/bf00210807. PMID 2338340. 
• "PU.1 (Spi-1) autoregulates its expression in myeloid cells". Oncogene 11 (8): 1549–1560. October 1995. PMID 7478579. 
• "Multiple proteins physically interact with PU.1. Transcriptional synergy with NF-IL6 beta (C/EBP delta, CRP3)". Journal of Immunology 155 (9): 4330–4338. November 1995. doi:10.4049/jimmunol.155.9.4330. PMID 7594592. 
• "Activating transcription factor 1 and cyclic AMP response element modulator can modulate the activity of the immunoglobulin kappa 3' enhancer". The Journal of Biological Chemistry 270 (17): 10304–10313. April 1995. doi:10.1074/jbc.270.17.10304. PMID 7730336. 
• "Hematopoietic lineage- and stage-restricted expression of the ETS oncogene family member PU.1". Blood 82 (10): 2998–3004. November 1993. doi:10.1182/blood.V82.10.2998.2998. PMID 8219191. 
• "The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB". Proceedings of the National Academy of Sciences of the United States of America 90 (4): 1580–1584. February 1993. doi:10.1073/pnas.90.4.1580. PMID 8434021. Bibcode: 1993PNAS...90.1580H. 
• "The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb". The Journal of Biological Chemistry 271 (19): 11177–11181. May 1996. doi:10.1074/jbc.271.19.11177. PMID 8626664. 
• "Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells". Journal of Virology 71 (5): 3563–3573. May 1997. doi:10.1128/JVI.71.5.3563-3573.1997. PMID 9094628. 
• "PU.1 is essential for p47(phox) promoter activity in myeloid cells". The Journal of Biological Chemistry 272 (28): 17802–17809. July 1997. doi:10.1074/jbc.272.28.17802. PMID 9211934. 
• "Human T-cell leukemia virus type I Tax transactivates the promoter of human prointerleukin-1beta gene through association with two transcription factors, nuclear factor-interleukin-6 and Spi-1". Blood 90 (8): 3142–3153. October 1997. doi:10.1182/blood.V90.8.3142. PMID 9376596. 
• "The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS". The Journal of Biological Chemistry 273 (9): 4838–4842. February 1998. doi:10.1074/jbc.273.9.4838. PMID 9478924. 
• "PU.1 as an essential activator for the expression of gp91(phox) gene in human peripheral neutrophils, monocytes, and B lymphocytes". Proceedings of the National Academy of Sciences of the United States of America 95 (11): 6085–6090. May 1998. doi:10.1073/pnas.95.11.6085. PMID 9600921. Bibcode: 1998PNAS...95.6085S. 
• "Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains". Oncogene 16 (25): 3261–3268. June 1998. doi:10.1038/sj.onc.1201868. PMID 9681824. 
• "Microphthalmia-associated transcription factor interacts with PU.1 and c-Fos: determination of their subcellular localization". Biochemical and Biophysical Research Communications 254 (2): 384–387. January 1999. doi:10.1006/bbrc.1998.9918. PMID 9918847. 
• "Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers". The EMBO Journal 18 (4): 977–991. February 1999. doi:10.1093/emboj/18.4.977. PMID 10022840. 
• "Physical and functional interactions between the transcription factor PU.1 and the coactivator CBP". Oncogene 18 (7): 1495–1501. February 1999. doi:10.1038/sj.onc.1202427. PMID 10050886. 
• "SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1". The Journal of Biological Chemistry 274 (16): 11115–11124. April 1999. doi:10.1074/jbc.274.16.11115. PMID 10196196. 
• "Functional and physical interactions between AML1 proteins and an ETS protein, MEF: implications for the pathogenesis of t(8;21)-positive leukemias". Molecular and Cellular Biology 19 (5): 3635–3644. May 1999. doi:10.1128/mcb.19.5.3635. PMID 10207087. 

External links

• FactorBook PU.1