Sp1 transcription factor
# Sp1 transcription factor

Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.

## Function

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, O-GlcNAcylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor.

In the SV40 virus, Sp1 binds to the GC boxes in the regulatory region (RR) of the genome.

## Structure

SP1 belongs to the Sp/KLF family of transcription factors. The protein is 785 amino acids long, with a molecular weight of 81 kDa. The SP1 transcription factor contains two glutamine-rich activation domains at its N-terminus that are believed to be necessary for promoter trans-activation. SP1 most notably contains three zinc finger protein motifs at its C-terminus, by which it binds directly to DNA and allows for interaction of the protein with other transcriptional regulators. Its zinc fingers are of the $Cys_2/His_2$ type and bind the consensus sequence 5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' (GC box element). Some 12,000 SP-1 binding sites are found in the human genome.

## Applications

Sp1 has been used as a control protein to compare with when studying the increase or decrease of the aryl hydrocarbon receptor and/or the estrogen receptor, since it binds to both and generally remains at a relatively constant level.

Recently, a putative promoter region in FTMT, and positive regulators {SP1, cAMP response element-binding protein (CREB), and Ying Yang 1 (YY1)] and negative regulators [GATA2, forkhead box protein A1 (FoxA1), and CCAAT enhancer-binding protein b (C/EBPb)] of FTMT transcription have been identified (Guaraldo et al, 2016).The effect of DFP on the DNA-binding activity of these regulators to the FTMT promoter was examined using chromatin immunoprecipitation (ChIP) assay. Among the regulators, only SP1 displayed significantly increased DNA- binding activity following DFP treatment in a dose-dependent manner. SP1 knockdown by siRNA abolished the DFP-induced increase in the mRNA levels of FTMT, indicating SP1-mediated regulation of FTMT expression in the presence of DFP. Treatment with Deferiprone increased the expression of cytoplasmic and nuclear SP1 with predominant localization in the nucleus.

## Inhibitors

Plicamycin, an antineoplastic antibiotic produced by Streptomyces plicatus, and Withaferin A, a steroidal lactone from Withania somnifera plant are known to inhibit Sp1 transcription factor.

miR-375-5p microRNA significantly decreased expression of SP1 and YAP1 in colorectal cancer cells. SP1 and YAP1 mRNAs are direct targets of miR-375-5p.

## Interactions

Sp1 transcription factor has been shown to interact with:

* AATF,
* CEBPB,
* COL1A1,
* E2F1,
* FOSL1,
* GABPA,
* HDAC1,
* HDAC2,
* HMGA1,
* HCFC1,
* HTT,
* KLF6,
* MEF2C,
* MEF2D,
* MSX1,
* Myogenin,
* POU2F1,
* PPP1R13L,
* PSMC5,
* PML,
* RELA,
* SMAD3,
* SUMO1,
* SF1,
* TAL1,
* UBC.
* WRN,
* DDX3X
