Sp1 (biology)
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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 A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. The term ''zinc finger'' was originally coined to describe the finger-like appearance of a ...
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 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 modification In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...
s 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 : In 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 opposite react ...
, ''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 is found to cause tumors in humans and animals, but most ofte ...
virus, Sp1 binds to the GC boxes in the
regulatory sequence A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and vir ...
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 A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
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 Cys2/His2 type and bind the
consensus sequence In molecular biology and bioinformatics, the consensus sequence (or canonical sequence) is the calculated sequence of most frequent residues, either nucleotide or amino acid, found at each position in a sequence alignment. It represents the result ...
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, AH receptor, or as the 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 express ...
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-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 (genetics), transcription of the ...
(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 ''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, butyrolac ...
'', and
Withaferin A Withaferin A is a steroidal lactone, derived from ''Acnistus arborescens'', ''Withania somnifera'' and other members of family Solanaceae. It is the first member of the withanolide class of ergostane type product to be discovered. Structure Wit ...
, a steroidal lactone from ''
Withania somnifera ''Withania somnifera'', known commonly as ashwagandha, is an evergreen shrub in the Solanaceae family that is native to the Middle East and North Africa, other African regions, southern Europe, and Indian subcontinent. Several other species in ...
'' 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 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 ...
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 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 ...
mRNAs are direct targets of miR-375-5p.


Interactions

Transcription factor Sp1 has been shown to interact 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 regi ...
, *
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 ...
, *
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 cel ...
, *
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 pro ...
, *
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 subun ...
, *
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. ...
, *
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 ...
, * HMGA1, *
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, *
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 l ...
, *
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 transcr ...
, *
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. Myogeni ...
, *
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 tra ...
, *
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 (protein), SMAD family of proteins. It acts as a mediator of the signal ...
, *
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 a ...
, * 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-l ...
, *
UBC The University of British Columbia (UBC) is a Public university, public research university with campuses near University of British Columbia Vancouver, Vancouver and University of British Columbia Okanagan, Kelowna, in British Columbia, Canada ...
. * WRN, *
DDX3X ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the ''DDX3X'' gene. Function DEAD box proteins are putative RNA helicases characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD). They are implicated in a numb ...


References


Further reading

* * * * * * * * * * * * * * * * * * * * * *


External links

* * {{NLM content Transcription factors