Molecule Information

General Information of the Molecule (ID: Mol04302)

• Name: STAM-binding protein (STAMBP) ,Homo sapiens
• Synonyms: Associated molecule with the SH3 domain of STAM ; Endosome-associated ubiquitin isopeptidase
• Molecule Type: Protein
• Gene Name: STAMBP
• Gene ID: 10617
• Sequence:
  MSDHGDVSLPPEDRVRALSQLGSAVEVNEDIPPRRYFRSGVEIIRMASIYSEEGNIEHAF
  ILYNKYITLFIEKLPKHRDYKSAVIPEKKDTVKKLKEIAFPKAEELKAELLKRYTKEYT
  E YNEEKKKEAEELARNMAIQQELEKEKQRVAQQKQQQLEQEQFHAFEEMIRNQELEKER
  LK IVQEFGKVDPGLGGPLVPDLEKPSLDVFPTLTVSSIQPSDCHTTVRPAKPPVVDRSL
  KPG ALSNSESIPTIDGLRHVVVPGRLCPQFLQLASANTARGVETCGILCGKLMRNEFTI
  THVL IPKQSAGSDYCNTENEEELFLIQDQQGLITLGWIHTHPTQTAFLSSVDLHTHCSY
  QMMLP ESVAIVCSPKFQETGFFKLTDHGLEEISSCRQKGFHPHSKDPPLFCSCSHVTVV
  DRAVTI TDLR
• Function: Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains . Does not cleave 'Lys-48'-linked polyubiquitin chains. Plays a role in signal transduction for cell growthand MYC induction mediated by IL-2 and GM-CSF .Potentiates BMP signaling by antagonizingthe inhibitory action of SMAD6 and SMAD7 . Has a keyrole in regulation of cell surface receptor-mediated endocytosis andubiquitin-dependent sorting of receptors to lysosomes . Endosomal localization of STAMBP is required forefficient EGFR degradation but not for its internalization. Involved in the negative regulationof PI3K-AKT-mTOR and RAS-MAP signaling pathways .{ECO:0000269|PubMed:10383417, ECO:0000269|PubMed:11483516,ECO:0000269|PubMed:15314065, ECO:0000269|PubMed:17261583,ECO:0000269|PubMed:23542699, ECO:0000269|PubMed:34425109}.
• Uniprot ID: STABP_HUMAN
• Ensembl ID: ENSG0000012435617
• HGNC ID: HGNC:16950

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

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Aerobic glycolysis signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: mitochondrial respiration signaling pathway; Regulation; N.A.
• In Vitro Model: AsPC1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• In Vitro Model: BxPc3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overall, we presented the first evidence that STAMBP expression is increased in PC-resistant tissues and is linked to the prognosis of patients with PC. We further showed that STAMBP leads to chemotherapy resistance in PC by increasing PDK1-mediated aerobic glycolysis. Our findings additionally demonstrated that STAMBP promotes the PDK1-mediated Warburg effect and chemotherapy resistance by modulating E2F1, which is achieved by binding directly to E2F1 and suppressing its degradation and ubiquitination . Importantly, entrectinib-mediated targeting of STAMBP enhanced the chemosensitivity of PC cells remarkably. Based on these findings, STAMBP was concluded to act against chemoresistance in PC by enhancing aerobic glycolysis mediated by E2F1/PDK1. Therefore, targeting the STAMBP/E2F1/PDK1 axis may be a promising therapeutic strategy for PC.

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Aerobic glycolysis signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: mitochondrial respiration signaling pathway; Regulation; N.A.
• In Vitro Model: CFPAC-1 cells; Pancreas; Homo sapiens (Human); CVCL_1119
• In Vitro Model: SW1990 cells; Pancreas; Homo sapiens (Human); CVCL_1723
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overall, we presented the first evidence that STAMBP expression is increased in PC-resistant tissues and is linked to the prognosis of patients with PC. We further showed that STAMBP leads to chemotherapy resistance in PC by increasing PDK1-mediated aerobic glycolysis. Our findings additionally demonstrated that STAMBP promotes the PDK1-mediated Warburg effect and chemotherapy resistance by modulating E2F1, which is achieved by binding directly to E2F1 and suppressing its degradation and ubiquitination . Importantly, entrectinib-mediated targeting of STAMBP enhanced the chemosensitivity of PC cells remarkably. Based on these findings, STAMBP was concluded to act against chemoresistance in PC by enhancing aerobic glycolysis mediated by E2F1/PDK1. Therefore, targeting the STAMBP/E2F1/PDK1 axis may be a promising therapeutic strategy for PC.

References

• Ref 1: Identification of STAM-binding protein as a target for the treatment of gemcitabine resistance pancreatic cancer in a nutrient-poor microenvironment. Cell Death Dis. 2024 Sep 6;15(9):657.