Molecule Information

General Information of the Molecule (ID: Mol01871)

• Name: Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) ,Homo sapiens
• Synonyms: EIF4EBP1
• Molecule Type: Protein
• Gene Name: EIF4EBP1
• Gene ID: 1978
• Location: chr8:38,030,534-38,060,365[+]
• Sequence:
  MSGGSSCSQTPSRAIPATRRVVLGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLM
  ECRNSPVTKTPPRDLPTIPGVTSPSSDEPPMEASQSHLRNSPEDKRAGGEESQFEMDI
• Function: Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.
• Uniprot ID: 4EBP1_HUMAN
• Ensembl ID: ENSG00000187840
• HGNC ID: HGNC:3288

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) 1 drug(s) in total

Everolimus

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pancreatic neuroendocrine tumor [1]

• Resistant Disease: Pancreatic neuroendocrine tumor [ICD-11: 2C10.1]
• Resistant Drug: Everolimus
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: CXCR4-CXCL12-CXCR7 signaling pathway; Activation; hsa04061
• In Vitro Model: A498 cells; Kidney; Homo sapiens (Human); CVCL_1056
• In Vitro Model: SN12C cells; Kidney; Homo sapiens (Human); CVCL_1705
• Experiment for Molecule Alteration: Western blotting assay
• Mechanism Description: When the CXCR4-CXCL12-CXCR7 pathway is activated through CXCL12 in human renal cancer cells were, SN12C and A498, CXCL12 induced the mTOR targets p-P70S6K and p-4EBP1.The combination therapy of mTOR inhibitors with the CXCR4-CXCL12-CXCR7 axis inhibitors in renal cancer tumors could overcome the Everolimus resistance.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.83E-01; Fold-change: 1.75E-01; Z-score: 1.67E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.69E-03; Fold-change: -4.52E-01; Z-score: -4.86E-01

References

• Ref 1: Everolimus and pancreatic neuroendocrine tumors (PNETs): Activity, resistance and how to overcome it .Int J Surg. 2015 Sep;21 Suppl 1:S89-94. doi: 10.1016/j.ijsu.2015.06.064. Epub 2015 Jun 27. 10.1016/j.ijsu.2015.06.064