SP1

Fig1. Protein structure of Sp1 with indicated domains and post-translational modifications. (Bo-Kun Yin, 2021)

What is SP1 protein?

SP1 gene (Sp1 transcription factor) is a protein coding gene which situated on the long arm of chromosome 12 at locus 12q13. The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. The SP1 protein is consisted of 785 amino acids and SP1 molecular weight is approximately 80.7 kDa.

What is the function of SP1 protein?

SP1 Protein, also known as Specificity Protein 1, is a transcription factor with multiple biological functions involved in key cellular processes such as cell growth, differentiation, apoptosis, immune response, DNA damage response, and chromatin remodeling. As a transcription factor, SP1 activates or inhibits the expression of a variety of genes involved in processes such as cell growth, differentiation, apoptosis, and immune response. SP1 is involved in controlling cell cycle and promoting cell proliferation by regulating the expression of related genes. SP1 may be involved in regulating cell response to DNA damage, influencing cell cycle checkpoints and DNA repair mechanisms. SP1 is involved in chromatin remodeling, affecting gene expression and regulation.

SP1 Related Signaling Pathway

SP1 binds to GC-rich motifs in the gene regulatory regions of these signaling pathways and is involved in the control of cell proliferation, differentiation, and death. The kinases in these signaling pathways can alter the transcriptional activity of SP1 through phosphorylation, affecting its binding efficiency to cofactors and DNA regulatory regions. As a non-receptor tyrosine kinase, JAK2 is involved in a variety of cellular processes, including cell cycle, apoptosis, mitotic recombination, etc. JAK2 is activated by ligand binding to related cytokine receptors, which in turn activates the STAT protein and is involved in signal transduction. As proto-oncogenes, c-Fos and c-Myc are involved in the regulation of cell proliferation and differentiation. SP1 is related to the activity and expression of these transcription factors, which in turn influence the physiological and pathological processes of cells.

SP1 Related Diseases

Studies have shown that deficiency of the transcription factor SP1 is associated with hypertrophic cardiomyopathy, and the deletion of SP1 produces the typical phenotypes of HCM in mouse models, including myocardial hypertrophy, interstitial fibrosis, and myofilament disorders. The expression level of SP1 in tumor cells is closely related to the occurrence, development and sensitivity of tumor to chemotherapy drugs. By promoting the transcriptional expression of GSDME, SP1 enhances the pyrodeath level of cells under stimulation conditions and affects the sensitivity of chemotherapy drugs. Including Huntington's disease, Parkinson's disease, etc., SP1 activity is associated with the pathogenesis of these diseases. SP1 has also been linked to prostate cancer, lung cancer, alcoholic hepatitis, myelodysplastic syndrome and other diseases.

Bioapplications of SP1

SP1 is a potential therapeutic target for a variety of diseases, and the development of small molecule inhibitors or activators targeting its function is ongoing, particularly in the field of cancer therapy. Changes in SP1 expression levels in certain diseases may serve as biomarkers for diagnosis and prognosis. Targeting SP1 with gene-editing techniques such as CRISPR/Cas9 could help develop new gene therapy strategies. As a transcription factor, SP1 plays an important role in transcriptional regulation in the study of cell response to external signals. The role of SP1 in the plasticity and immune memory of disease-associated microglia provides a new perspective for studying immune regulation in central nervous system diseases.

Case Study 1: Kincaid Rowbotham, 2020

SP1 binding in SV40 chromatin in vitro and in vivo was characterized in order to better understand its role during the initiation of early transcription. Researchers observed that chromatin from disrupted virions, but not minichromosomes, was efficiently bound by HIS-tagged SP1 in vitro, while the opposite was true for the presence of endogenous SP1 introduced in vivo. Using ChIP-Seq to compare the location of SP1 to nucleosomes carrying modified histones, they found that SP1 could occupy its whole binding site in virion chromatin but only the early side of its binding site in most of the minichromosomes carrying modified histones due to the presence of overlapping nucleosomes. The results suggest that during the initiation of an SV40 infection, SP1 binds to an open region in SV40 virion chromatin but quickly triggers chromatin reorganization and its own removal.

Fig1. Binding of HIS-tagged SP1 to SV40 chromatin from disrupted virions and minichromosomes.

Fig2. Presence of HH3, HH4, H3K9me1, and H3K9me3 in chromatin from disrupted virions bound by HIS-tagged SP1.

Case Study 2: Yuan Fang, 2024

Hepatocellular carcinoma (HCC) is characterized by aggressive progression and elevated mortality rates. This study aimed to investigate the regulatory effects of RBBP7 on HCC pathogenesis and the underlying mechanisms. The regulatory effect of transcription factors of specificity protein 1 (SP1) on RBBP7 mRNA expression was confirmed in dual-luciferase reporter assays and chromatin immunoprecipitation experiments. The outcomes of the dual-luciferase assay further confirmed that SP1 is capable of activating the promoter of RBBP7.

Fig3. SP1 upregulation was established in the Hep3B.

Fig4. RBBP7 expression was test by western blotting and RT-qPCR in SP1 rescue experiments.

SP1 has several biochemical functions, for example, DNA binding,HMG box domain binding,RNA polymerase II core promoter proximal region sequence-specific DNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SP1 itself. We selected most functions SP1 had, and list some proteins which have the same functions with SP1. You can find most of the proteins on our site.

SP1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SP1 here. Most of them are supplied by our site. Hope this information will be useful for your research of SP1.

POU2F1;STAT3;HCFC1;SREBF2;tf65_human_gc-box3_dna-probe