Molecule Information

General Information of the Molecule (ID: Mol04401)

• Name: Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) ,Homo sapiens
• Synonyms: Phosphorylated heat- and acid-stable protein regulated by insulin 1
• Molecule Type: Protein
• Gene Name: EIF4EBP1
• Gene ID: 1978
• Sequence:
  MSGGSSCSQTPSRAIPATRRVVLGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLM
  ECRNSPVTKTPPRDLPTIPGVTSPSSDEPPMEASQSHLRNSPEDKRAGGEESQFEMDI
• Function: Repressor of translation initiation that regulates EIF4Eactivity by preventing its assembly into the eIF4F complex:hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly bindsto EIF4E, leading to repress translation. In contrast,hyperphosphorylated form dissociates from EIF4E, allowing interactionbetween EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation.Mediates the regulation of protein translation by hormones, growthfactors and other stimuli that signal through the MAP kinase and mTORC1pathways. {ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22684010,ECO:0000269|PubMed:7935836}.
• Uniprot ID: 4EBP1_HUMAN
• Ensembl ID: ENSG000001878405
• 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

Alpelisib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Head and neck cancer [ICD-11: 2D42.0] [1]

• Sensitive Disease: Head and neck cancer [ICD-11: 2D42.0]
• Sensitive Drug: Alpelisib
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: Cal-33 cells; Tongue; Homo sapiens (Human); CVCL_1108
• In Vitro Model: FaDu cells; Pharynx; Homo sapiens (Human); CVCL_1218
• In Vitro Model: HSC-4 cells; Cervical lymph node; Homo sapiens (Human); CVCL_1289
• In Vitro Model: SAS cells; Oral; Homo sapiens (Human); CVCL_1675
• In Vitro Model: UT-SCC-5 cells; Head and Neck; Homo sapiens (Human); CVCL_7858
• In Vitro Model: UT-SCC-8 cells; Head and Neck; Homo sapiens (Human); CVCL_7869
• In Vitro Model: UT-SCC-14 cells; Head and Neck; Homo sapiens (Human); CVCL_7810
• In Vitro Model: UT-SCC-15 cells; Head and Neck; Homo sapiens (Human); CVCL_7811
• Experiment for Molecule Alteration: Whole exome sequencing assay; Western blot assay; Akt activity assay; 3D foci assay; Phosphorylation pathway analysis; Gene enrichment assay; Network analysis; Functional enrichment analysis
• Experiment for Drug Resistance: 3D colony formation assay
• Mechanism Description: In terms of PI3K/Akt pathway activity, Alpelisib treatment reduced phosphorylation of Akt (Ser473), GSK3beta (Ser9) and 4E-BP1 (Ser65) to a similar extent in responder and non-responder cell models (Fig. 2A, B and S2). Likewise, Akt activity was not significantly modified upon Alpelisib exposure (Fig. 2C). Taken together, our data show that inhibition of PI3Kalpha kinase causes varying degrees of radiochemosensitization in different HNSCC models and without an obvious mutational biomarker to predict drug effect.

References

• Ref 1: beta1 integrin mediates unresponsiveness to PI3Kalpha inhibition for radiochemosensitization of 3D HNSCC models. Biomed Pharmacother. 2024 Feb;171:116217.