Molecule Information

General Information of the Molecule (ID: Mol04170)

• Name: Thioredoxin interacting protein (TXNIP) ,Homo sapiens
• Synonyms: Thioredoxin-binding protein 2; Vitamin D3 up-regulated protein 1
• Molecule Type: Protein
• Gene Name: TXNIP
• Gene ID: 10628
• Location: chr1:145992435-145996579[-]
• Sequence:
  MVMFKKIKSFEVVFNDPEKVYGSGEKVAGRVIVEVCEVTRVKAVRILACGVAKVLWMQGS
  QQCKQTSEYLRYEDTLLLEDQPTGENEMVIMRPGNKYEYKFGFELPQGPLGTSFKGKYGC
  VDYWVKAFLDRPSQPTQETKKNFEVVDLVDVNTPDLMAPVSAKKEKKVSCMFIPDGRVSV
  SARIDRKGFCEGDEISIHADFENTCSRIVVPKAAIVARHTYLANGQTKVLTQKLSSVRGN
  HIISGTCASWRGKSLRVQKIRPSILGCNILRVEYSLLIYVSVPGSKKVILDLPLVIGSRS
  GLSSRTSSMASRTSSEMSWVDLNIPDTPEAPPCYMDVIPEDHRLESPTTPLLDDMDGSQD
  SPIFMYAPEFKFMPPPTYTEVDPCILNNNVQ
• 3D-structure: PDB ID: 5DWS; Classification: Ligase; Method: X-ray diffraction; Resolution: 1.65 Å
• Function: May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability (PubMed:17603038). Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm (By similarity). Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest (PubMed:12821938). Required for the maturation of natural killer cells (By similarity). Acts as a suppressor of tumor cell growth (PubMed:18541147). Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1) (PubMed:21460850). .
• Uniprot ID: TXNIP_HUMAN
• Ensembl ID: ENSG00000265972
• HGNC ID: HGNC:16952

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

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

Imatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Imatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: kCL22 cells; Pleural effusion; Homo sapiens (Human); CVCL_2091
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Here, we demonstrate that TXNIP expression was decreased in response to the activated BCR-ABL signaling, which is associated with a previously unappreciated mechanism that involves in c-Myc/Miz-1/P300 complex. Restoration of TXNIP expression sensitizes CML cells to imatinib treatment, potentially through the blockage of glucose metabolism. In particular, TXNIP suppressed glycolytic enzyme expressions through Fbw7-dependent c-Myc degradation. BCR-ABL suppression of TXNIP provided a novel survival pathway for CML transformation.

Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Imatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Nude mice, with K562 cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell colony formation assay
• Mechanism Description: Here, we demonstrate that TXNIP expression was decreased in response to the activated BCR-ABL signaling, which is associated with a previously unappreciated mechanism that involves in c-Myc/Miz-1/P300 complex. Restoration of TXNIP expression sensitizes CML cells to imatinib treatment, potentially through the blockage of glucose metabolism. In particular, TXNIP suppressed glycolytic enzyme expressions through Fbw7-dependent c-Myc degradation. BCR-ABL suppression of TXNIP provided a novel survival pathway for CML transformation.

References

• Ref 1: BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP. Cell Death Dis. 2023 Apr 24;14(4):287.