Molecule Information

General Information of the Molecule (ID: Mol04440)

• Name: GSK3B-interacting protein (GSKIP) ,Homo sapiens
• Synonyms: GSK3beta interaction protein
• Molecule Type: Protein
• Gene Name: GSKIP
• Gene ID: 51527
• Sequence:
  METDCNPMELSSMSGFEEGSELNGFEGTDMKDMRLEAEAVVNDVLFAVNNMFVSKSLRCA
  DDVAYINVETKERNRYCLELTEAGLKVVGYAFDQVDDHLQTPYHETVYSLLDTLSPAYR
  E AFGNALLQRLEALKRDGQS
• Function: A-kinase anchoring protein for GSK3B and PKA that regulatesor facilitates their kinase activity towards their targets. The ternarycomplex enhances Wnt-induced signaling by facilitating the GSK3B- andPKA-induced phosphorylation of beta-catenin leading to beta-catenindegradation and stabilization respectively . Upon cAMP activation, the ternary complex contributesto neuroprotection against oxidative stress-induced apoptosis byfacilitating the PKA-induced phosphorylation of DML1 and PKA-inducedinactivation of GSK3B . During neurite outgrowthpromotes neuron proliferation; while increases beta-catenin-inducedtranscriptional activity through GSK3B kinase activity inhibition,reduces N-cadherin level to promote cell cycle progression. {ECO:0000269|PubMed:16981698,ECO:0000269|PubMed:19830702, ECO:0000269|PubMed:25920809,ECO:0000269|PubMed:27484798}.
• Uniprot ID: GSKIP_HUMAN
• Ensembl ID: ENSG0000010074415
• HGNC ID: HGNC:20343

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.