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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the SP1
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
The protein encoded by this gene is a
zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
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 grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, immune responses, response to DNA damage, and
chromatin remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...
.
Post-translational modifications
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosomes ...
such as
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
,
acetylation
:
In organic chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply '' acetates''. Deacetylation is the oppo ...
,
''O''-GlcNAcylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor.
In the
SV40
SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often ...
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
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
long, with a
molecular weight
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
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
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized structu ...
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
In molecular biology and bioinformatics, the consensus sequence (or canonical sequence) is the calculated order of most frequent residues, either nucleotide or amino acid, found at each position in a sequence alignment. It serves as a simplified r ...
5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' (
GC box In molecular biology, a GC box, also known as a GSG box, is a distinct pattern of nucleotides found in the promoter region of some eukaryotic genes. The GC box is upstream of the TATA box, and approximately 110 bases upstream from the transcription ...
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
The aryl hydrocarbon receptor (also known as AhR, AHR, ahr, ahR, or dioxin receptor) is a protein that in humans is encoded by the AHR gene. The aryl hydrocarbon receptor is a transcription factor that regulates gene expression. It was originall ...
and/or the
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
, 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-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first des ...
(CREB), and Ying Yang 1 (
YY1
YY1 (Yin Yang 1) is a transcriptional repressor protein in humans that is encoded by the YY1 gene.
Function
YY1 is a ubiquitously distributed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins. The protein is invo ...
)] 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
''Streptomyces rochei'' is a bacterium species from the genus of '' Streptomyces'' which has been isolated from soil in Russia.Deutsche Sammlung von Mikroorganismen und Zellkulturenbr>/ref> ''Streptomyces rochei'' produces borrelidin, butyrola ...
'', and
Withaferin A, a steroidal lactone from ''
Withania somnifera
''Withania somnifera'', known commonly as ashwagandha or winter cherry, is an evergreen shrub in the Solanaceae or nightshade family that grows in India, the Middle East, and parts of Africa. Several other species in the genus ''Withania'' are m ...
'' plant are known to inhibit Sp1 transcription factor.
miR-375-5p
microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
significantly decreased expression of SP1 and
YAP1
YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in th ...
in
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
cells. SP1 and
YAP1
YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in th ...
mRNAs
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the p ...
are direct targets of miR-375-5p.
Interactions
Sp1 transcription factor has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
AATF,
[
* ]CEBPB
CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the ''CEBPB'' gene.
Function
The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regio ...
,
* COL1A1
Collagen, type I, alpha 1, also known as alpha-1 type I collagen, is a protein that in humans is encoded by the gene. ''COL1A1'' encodes the major component of type I collagen, the fibrillar collagen found in most connective tissues, including c ...
,
* E2F1
Transcription factor E2F1 is a protein that in humans is encoded by the ''E2F1'' gene.
Function
The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell ...
,
* FOSL1
Fos-related antigen 1 (FRA1) is a protein that in humans is encoded by the ''FOSL1'' gene.
Function
The Fos gene family consists of 4 members: c-Fos, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with prot ...
,
* GABPA
GA-binding protein alpha chain is a protein that in humans is encoded by the ''GABPA'' gene.
Function
This gene encodes one of three GA-binding protein transcription factor subunits which functions as a DNA-binding subunit. Since this subunit ...
,
* HDAC1
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene.
Function
Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. T ...
,
* HDAC2
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the co ...
,
* HMGA1
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the ''HMGA1'' gene.
Function
This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transc ...
,[
* ]HCFC1
Host cell factor 1 (HCFC1, HCF1, or HCF-1), also known as VP16-accessory protein, is a protein that in humans is encoded by the ''HCFC1'' gene.
Structure
HCF1 is a member of the highly conserved host cell factor family and encodes a protein wi ...
,
* HTT,
* KLF6
Krueppel-like factor 6 is a protein that in humans is encoded by the ''KLF6'' gene.
It is a tumor suppressor gene.
Function
This gene encodes a nuclear protein that has three zinc fingers at the end of its C-terminal domain, a serine/threonin ...
,
* MEF2C
Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the ''MEF2C'' gene. MEF2C is a transcription factor in the Mef2 family.
Genomics
The gene is lo ...
,
* MEF2D
Myocyte-specific enhancer factor 2D is a protein that in humans is encoded by the ''MEF2D'' gene.
Interactions
MEF2D has been shown to interact with:
* CABIN1,
* EP300,
* MAPK7,
* Myocyte-specific enhancer factor 2A,
* NFATC2
* Sp1 transcript ...
,
* MSX1
Homeobox protein MSX-1, is a protein that in humans is encoded by the ''MSX1'' gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue ...
,
* 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. Myogenin is ...
,
* POU2F1
POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene.
Interactions
POU2F1 has been shown to interact with:
* EPRS,
* Glucocorticoid receptor,
* Glyceraldehyde 3-phosphate dehydrogenase,
...
,
* PPP1R13L,
* PSMC5
26S protease regulatory subunit 8, also known as 26S proteasome AAA-ATPase subunit Rpt6, is an enzyme that in humans is encoded by the ''PSMC5'' gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex ...
,
* PML,
* RELA
Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene.
RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear tran ...
,
* SMAD3
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.
SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by t ...
,
* SUMO1
Small ubiquitin-related modifier 1 is a protein that in humans is encoded by the ''SUMO1'' gene.
Function
This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It is a ubiquitin-like protein an ...
,
* SF1,
* TAL1
__NOTOC__
T-cell acute lymphocytic leukemia protein 1 (i.e. TAL1 but also termed stem cell leukemia/T-cell acute leukemia 1 .e. SCL/TAL1 is a protein that in humans is encoded by the ''TAL1'' gene.
The protein encoded by TAL1 is a basic helix-lo ...
,
* UBC
The University of British Columbia (UBC) is a public research university with campuses near Vancouver and in Kelowna, British Columbia. Established in 1908, it is British Columbia's oldest university. The university ranks among the top three ...
.
* WRN,
* DDX3X
ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the ''DDX3X'' gene.
Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a numbe ...
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
*
*
{{NLM content
Transcription factors