Transcription factor Sp1

Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.[5]

SP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSP1, entrez:6667, Sp1 transcription factor
External IDsOMIM: 189906 MGI: 98372 HomoloGene: 8276 GeneCards: SP1
Orthologs
SpeciesHumanMouse
Entrez

6667

20683

Ensembl

ENSG00000185591

ENSMUSG00000001280

UniProt

P08047

O89090

RefSeq (mRNA)

NM_001251825
NM_003109
NM_138473

NM_013672

RefSeq (protein)

NP_001238754
NP_003100
NP_612482

NP_038700

Location (UCSC)Chr 12: 53.38 – 53.42 MbChr 15: 102.31 – 102.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

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 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.[6] 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 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.[7]

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.[8]

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.[9]

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.[10][11]

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.[12]

Interactions

Transcription factor Sp1 has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000185591 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000001280 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: Sp1 transcription factor".
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Further reading

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