Molecule Information

General Information of the Molecule (ID: Mol00228)

• Name: Transcription factor AP2 alpha (TFAP2A) ,Homo sapiens
• Synonyms: AP2-alpha; AP-2 transcription factor; Activating enhancer-binding protein 2-alpha; Activator protein 2; AP-2; AP2TF; TFAP2
• Molecule Type: Protein
• Gene Name: TFAP2A
• Gene ID: 7020
• Location: chr6:10393186-10419659[-]
• Sequence:
  MLWKLTDNIKYEDCEDRHDGTSNGTARLPQLGTVGQSPYTSAPPLSHTPNADFQPPYFPP
  PYQPIYPQSQDPYSHVNDPYSLNPLHAQPQPQHPGWPGQRQSQESGLLHTHRGLPHQLSG
  LDPRRDYRRHEDLLHGPHALSSGLGDLSIHSLPHAIEEVPHVEDPGINIPDQTVIKKGPV
  SLSKSNSNAVSAIPINKDNLFGGVVNPNEVFCSVPGRLSLLSSTSKYKVTVAEVQRRLSP
  PECLNASLLGGVLRRAKSKNGGRSLREKLDKIGLNLPAGRRKAANVTLLTSLVEGEAVHL
  ARDFGYVCETEFPAKAVAEFLNRQHSDPNEQVTRKNMLLATKQICKEFTDLLAQDRSPLG
  NSRPNPILEPGIQSCLTHFNLISHGFGSPAVCAAVTALQNYLTEALKAMDKMYLSNNPNS
  HTDNNAKSSDKEEKHRK
• Function: Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region.
• Uniprot ID: AP2A_HUMAN
• Ensembl ID: ENSG00000137203
• HGNC ID: HGNC:11742

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Cervical cancer [1]

• Resistant Disease: Cervical cancer [ICD-11: 2C77.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Clonogenic assay
• Mechanism Description: The transcription factor AP-2alpha functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2alpha, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. miR-200b/200c/429 family recognized the MRE in the 3' UTR of AP-2alpha gene and negatively regulated the expression of endogenous AP-2alpha proteins.

Disease Class: Endometrial cancer [1]

• Resistant Disease: Endometrial cancer [ICD-11: 2C76.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEC-1A cells; Uterus; Homo sapiens (Human); CVCL_0293
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Clonogenic assay
• Mechanism Description: The transcription factor AP-2alpha functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2alpha, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. miR-200b/200c/429 family recognized the MRE in the 3' UTR of AP-2alpha gene and negatively regulated the expression of endogenous AP-2alpha proteins.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [2]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR135a-5p/AP2alpha /BCL2 signaling pathway; Regulation; hsa05206
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: AP-2alpha contains a putative miRNA-135a-5p target, which was confirmed as a direct target using the 3'-UTR luciferase reporter system. Additionally, an increase and decrease of miRNA-135a-5p inhi bited or impaired adriamycin-induced apoptosis in BGC-823 cells (p<0.05, compared with the group without gene intervention), respectively. Luciferase reporter experiments confirmed that AP-2alpha bound to the BCL-2 promoter and affected its transcription. Therefore, miRNA-135a-5p increased BCL-2 via AP-2alpha and consequently (+) cell resistance to apoptosis.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.20E-01; Fold-change: 5.29E-03; Z-score: 2.94E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.08E-07; Fold-change: 2.24E-01; Z-score: 1.09E+00

Cervical cancer [ICD-11: 2C77]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Cervix uteri
• The Specified Disease: Cervical cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.84E-05; Fold-change: 2.11E-01; Z-score: 5.29E-01

References

• Ref 1: A miR-200b/200c/429-binding site polymorphism in the 3' untranslated region of the AP-2Alpha gene is associated with cisplatin resistance. PLoS One. 2011;6(12):e29043. doi: 10.1371/journal.pone.0029043. Epub 2011 Dec 14.
• Ref 2: Regulation of BGC-823 cell sensitivity to adriamycin via miRNA-135a-5p. Oncol Rep. 2014 Dec;32(6):2549-56. doi: 10.3892/or.2014.3546. Epub 2014 Oct 14.