Molecule Information

General Information of the Molecule (ID: Mol00646)

• Name: Transcription factor Sp1 (SP1) ,Homo sapiens
• Synonyms: TSFP1
• Molecule Type: Protein
• Gene Name: SP1
• Gene ID: 6667
• Location: chr12:53380176-53416446[+]
• Sequence:
  MSDQDHSMDEMTAVVKIEKGVGGNNGGNGNGGGAFSQARSSSTGSSSSTGGGGQESQPSP
  LALLAATCSRIESPNENSNNSQGPSQSGGTGELDLTATQLSQGANGWQIISSSSGATPTS
  KEQSGSSTNGSNGSESSKNRTVSGGQYVVAAAPNLQNQQVLTGLPGVMPNIQYQVIPQFQ
  TVDGQQLQFAATGAQVQQDGSGQIQIIPGANQQIITNRGSGGNIIAAMPNLLQQAVPLQG
  LANNVLSGQTQYVTNVPVALNGNITLLPVNSVSAATLTPSSQAVTISSSGSQESGSQPVT
  SGTTISSASLVSSQASSSSFFTNANSYSTTTTTSNMGIMNFTTSGSSGTNSQGQTPQRVS
  GLQGSDALNIQQNQTSGGSLQAGQQKEGEQNQQTQQQQILIQPQLVQGGQALQALQAAPL
  SGQTFTTQAISQETLQNLQLQAVPNSGPIIIRTPTVGPNGQVSWQTLQLQNLQVQNPQAQ
  TITLAPMQGVSLGQTSSSNTTLTPIASAASIPAGTVTVNAAQLSSMPGLQTINLSALGTS
  GIQVHPIQGLPLAIANAPGDHGAQLGLHGAGGDGIHDDTAGGEEGENSPDAQPQAGRRTR
  REACTCPYCKDSEGRGSGDPGKKKQHICHIQGCGKVYGKTSHLRAHLRWHTGERPFMCTW
  SYCGKRFTRSDELQRHKRTHTGEKKFACPECPKRFMRSDHLSKHIKTHQNKKGGPGVALS
  VGTLPLDSGAGSEGSGTATPSALITTNMVAMEAICPEGIARLANSGINVMQVADLQSINI
  SGNGF
• Function: Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component ARNTL/BMAL1. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112.
• Uniprot ID: SP1_HUMAN
• Ensembl ID: ENSG00000185591
• HGNC ID: HGNC:11205

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [1]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: MCF-7/ADM cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: A2780/PTX cells; Ovary; Homo sapiens (Human); CVCL_IJ13
• In Vitro Model: HOEC cells; Ovary; Homo sapiens (Human); N.A.
• In Vitro Model: SkOV3/PTX cells; Ovary; Homo sapiens (Human); CVCL_HF69
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-145 modulates the cellular response to anticancer drugs, Down-regulation of miR-145 is correlated with overexpression of Sp1 and Cdk6, Sp1 and Cdk6 are targets of miR-145, miR-145 downregulated P-gp and pRb through inhibition of Sp1 and Cdk6, miR-145 sensitized EOC cells to paclitaxel via Sp1 and Cdk6 inhibition, Overexpression of miR-145 enhanced paclitaxel sensitivity in vivo.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Malignant glioma [2]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: DNA damage repair signaling pathway; Activation; hsa03410
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: U118 cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: NHA; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; BrdU incorporation assay
• Mechanism Description: XIST was inversely correlated with miR29c, positively correlated with PS1, positively related with MGMT. XIST can inhibit miR29c expression by directly binding to miR29c and subsequently up-regulate the expression of SP1 and MGMT to promote the chemoresistance of glioma cells to TMZ.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioma [3]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: DNA mismatch repair pathway; Regulation; hsa03430
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Ectopic expression of miR-29c increased TMZ sensitivity by inhibiting cell growth and promoting apoptosis in U251/TR cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.59E-26; Fold-change: 3.07E-01; Z-score: 5.36E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.80E-02; Fold-change: 2.52E-01; Z-score: 3.08E+00
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.02E-03; Fold-change: 7.28E-01; Z-score: 1.40E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.21E-02; Fold-change: -1.23E-01; Z-score: -5.16E-01

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.36E-01; Fold-change: 5.65E-02; Z-score: 8.97E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.44E-06; Fold-change: 8.21E-01; Z-score: 1.66E+00

References

• Ref 1: miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6. Int J Cancer. 2014 Sep 15;135(6):1286-96. doi: 10.1002/ijc.28774. Epub 2014 Apr 28.
• Ref 2: LncRNA-XIST interacts with miR-29c to modulate the chemoresistance of glioma cell to TMZ through DNA mismatch repair pathway. Biosci Rep. 2017 Sep 7;37(5):BSR20170696. doi: 10.1042/BSR20170696. Print 2017 Oct 31.
• Ref 3: miR-29c contribute to glioma cells temozolomide sensitivity by targeting O6-methylguanine-DNA methyltransferases indirectely. Oncotarget. 2016 Aug 2;7(31):50229-50238. doi: 10.18632/oncotarget.10357.