Transcription factor Sp1, also known as specificity protein 1* is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''SP1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
The protein encoded by this gene is a
zinc finger transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth,
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
, immune responses, response to DNA damage, and
chromatin remodeling.
post-translational modifications such as
phosphorylation
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
,
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 sequence of the genome.
Structure
SP1 belongs to the
Sp/KLF family of transcription factors. The protein is 785
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
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
Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
, 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
ATA2, forkhead box protein A1 (FoxA1), and CCAAT enhancer-binding protein b (C/EBPb)">(FoxA1).html" ;"title="ATA2, forkhead box protein A1 (FoxA1)">ATA2, 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
Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...
significantly decreased expression of SP1 and
YAP1 in
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
cells. SP1 and
YAP1 mRNAs are direct targets of miR-375-5p.
Interactions
Transcription factor Sp1 has been shown to
interact with:
*
AATF,
[
* CEBPB,][
* HCFC1,]Myogenin
Myogenin, is a transcriptional activator encoded by the ''MYOG'' gene.
Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogeni ...
,
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
*
*
{{NLM content
Transcription factors