Molecule Information

General Information of the Molecule (ID: Mol01948)

• Name: Dishevelled binding antagonist of beta catenin 1 (DACT1) ,Mus musculus
• Synonyms: Ctnnb1; Catnb
• Molecule Type: Protein
• Gene Name: DACT1
• Gene ID: 12387
• Location: chr9:120,758,282-120,789,573[+]
• Sequence:
  MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTS
  QVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPT
  NVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSK
  KEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPAL
  VKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDC
  LQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEA
  GGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCA
  AGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEM
  AQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLL
  VRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFV
  QLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLF
  RMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEALGYRQDDPSYRSFH
  SGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTD
  L
• Function: Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle. Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling.
• Uniprot ID: CTNB1_MOUSE
• Ensembl ID: ENSMUSG00000006932
• HGNC ID: HGNC:17748

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: 9989
Family: Muridae
Genus: Mus
Species: Mus musculus

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Rabeprazole

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Glioma [1]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Rabeprazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: AKT/GSK3beta signaling pathway; Inhibition; hsa04931
• Cell Pathway Regulation: NF-KappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: MDA-231 cells; Pleural effusion; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MJ cells; Peripheral blood; Homo sapiens (Human); CVCL_1414
• In Vitro Model: MMQ cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_2117
• In Vitro Model: MOLM-13 cells; Peripheral blood; Homo sapiens (Human); CVCL_2119
• In Vivo Model: Male Wistar rats-Stereotaxic glioma model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blotting analysis; Gene expression analysis
• Experiment for Drug Resistance: MTT assay; Scratch wound healing migration assay; Transwell invasion assay
• Mechanism Description: Epithelial to mesenchymal transition (EMT) is pivotal in embryonic development and wound healing, whereas in cancer it inflicts malignancy and drug resistance. Rabeprazole has efficacy per se and reduces resistance to temozolomide in glioma via EMT inhibition. Rabeprazole suppressed EMT by impeding AKT/GSK3beta phosphorylation and/or NF-kappaB signaling and sensitized temozolomide resistance.

References

• Ref 1: Rabeprazole has efficacy per se and reduces resistance to temozolomide in glioma via EMT inhibition .Cell Oncol (Dordr). 2021 Aug;44(4):889-905. doi: 10.1007/s13402-021-00609-w. Epub 2021 May 4. 10.1007/s13402-021-00609-w