Molecule Information

General Information of the Molecule (ID: Mol00337)

• Name: Transcription factor E2F2 (E2F2) ,Homo sapiens
• Synonyms: E2F-2
• Molecule Type: Protein
• Gene Name: E2F2
• Gene ID: 1870
• Location: chr1:23506438-23531233[-]
• Sequence:
  MLQGPRALASAAGQTPKVVPAMSPTELWPSGLSSPQLCPATATYYTPLYPQTAPPAAAPG
  TCLDATPHGPEGQVVRCLPAGRLPAKRKLDLEGIGRPVVPEFPTPKGKCIRVDGLPSPKT
  PKSPGEKTRYDTSLGLLTKKFIYLLSESEDGVLDLNWAAEVLDVQKRRIYDITNVLEGIQ
  LIRKKAKNNIQWVGRGMFEDPTRPGKQQQLGQELKELMNTEQALDQLIQSCSLSFKHLTE
  DKANKRLAYVTYQDIRAVGNFKEQTVIAVKAPPQTRLEVPDRTEDNLQIYLKSTQGPIEV
  YLCPEEVQEPDSPSEEPLPSTSTLCPSPDSAQPSSSTDPSIMEPTASSVPAPAPTPQQAP
  PPPSLVPLEATDSLLELPHPLLQQTEDQFLSPTLACSSPLISFSPSLDQDDYLWGLEAGE
  GISDLFDSYDLGDLLIN
• Function: Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from g1 to s phase. E2F2 binds specifically to RB1 in a cell-cycle dependent manner.
• Uniprot ID: E2F2_HUMAN
• Ensembl ID: ENSG00000007968
• HGNC ID: HGNC:3114

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) 4 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: NRAS and E2F2 as the direct targets of miR-26a were further confirmed in luciferase activity assays and miR-26a-mediated these two genes expression analysis. Our results also found that knockdown of NRAS or E2F2 sensitize GC cells to cisplatin. miR-26a overexpression has been demonstrated to improve the sensitivity of GC cells to cisplatin and this effect was considered to be mediated via its targets NRAS and E2F2.

LY2835219

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: LY2835219
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The overexpression of E2F causes the cell to circumvent CDK4/6 inhibition and rely upon signaling pathways other than the cyclin D-CDK4/6 axis for cell cycle progression. Further studies are required to explore the detailed mechanism of this escape pathway. Moreover, inhibition of proteins downstream of E2F, in concert with CDK4/6 inhibition, may increase the efficacy of CDK4/6 inhibitors, overcoming resistance.

Palbociclib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Palbociclib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The overexpression of E2F causes the cell to circumvent CDK4/6 inhibition and rely upon signaling pathways other than the cyclin D-CDK4/6 axis for cell cycle progression. Further studies are required to explore the detailed mechanism of this escape pathway. Moreover, inhibition of proteins downstream of E2F, in concert with CDK4/6 inhibition, may increase the efficacy of CDK4/6 inhibitors, overcoming resistance.

Ribociclib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Ribociclib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The overexpression of E2F causes the cell to circumvent CDK4/6 inhibition and rely upon signaling pathways other than the cyclin D-CDK4/6 axis for cell cycle progression. Further studies are required to explore the detailed mechanism of this escape pathway. Moreover, inhibition of proteins downstream of E2F, in concert with CDK4/6 inhibition, may increase the efficacy of CDK4/6 inhibitors, overcoming resistance.

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: 4.44E-02; Fold-change: 2.37E-01; Z-score: 2.50E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.52E-04; Fold-change: 2.30E-01; Z-score: 7.57E-01

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.60E-01; Fold-change: -1.40E-02; Z-score: -6.47E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.04E-01; Fold-change: 7.94E-02; Z-score: 2.99E-01

References

• Ref 1: MiR-26a enhances the sensitivity of gastric cancer cells to cisplatin by targeting NRAS and E2F2. Saudi J Gastroenterol. 2015 Sep-Oct;21(5):313-9. doi: 10.4103/1319-3767.166206.
• Ref 2: Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review .Int J Cancer. 2019 Sep 1;145(5):1179-1188. doi: 10.1002/ijc.32020. Epub 2019 Jan 7. 10.1002/ijc.32020