Molecule Information

General Information of the Molecule (ID: Mol04151)

• Name: Polypyrimidine tract binding protein 1 (PTBP1) ,Homo sapiens
• Synonyms: 57 kDa RNA-binding protein PPTB-1; Heterogeneous nuclear ribonucleoprotein I
• Molecule Type: Protein
• Gene Name: PTBP1
• Gene ID: 5725
• Location: chr19:797075-812327[+]
• Sequence:
  MDGIVPDIAVGTKRGSDELFSTCVTNGPFIMSSNSASAANGNDSKKFKGDSRSAGVPSRV
  IHIRKLPIDVTEGEVISLGLPFGKVTNLLMLKGKNQAFIEMNTEEAANTMVNYYTSVTPV
  LRGQPIYIQFSNHKELKTDSSPNQARAQAALQAVNSVQSGNLALAASAAAVDAGMAMAGQ
  SPVLRIIVENLFYPVTLDVLHQIFSKFGTVLKIITFTKNNQFQALLQYADPVSAQHAKLS
  LDGQNIYNACCTLRIDFSKLTSLNVKYNNDKSRDYTRPDLPSGDSQPSLDQTMAAAFGAP
  GIISASPYAGAGFPPTFAIPQAAGLSVPNVHGALAPLAIPSAAAAAAAAGRIAIPGLAGA
  GNSVLLVSNLNPERVTPQSLFILFGVYGDVQRVKILFNKKENALVQMADGNQAQLAMSHL
  NGHKLHGKPIRITLSKHQNVQLPREGQEDQGLTKDYGNSPLHRFKKPGSKNFQNIFPPSA
  TLHLSNIPPSVSEEDLKVLFSSNGGVVKGFKFFQKDRKMALIQMGSVEEAVQALIDLHNH
  DLGENHHLRVSFSKSTI
• 3D-structure: PDB ID: 2ADC; Classification: Rna binding protein/rna; Method: Solution nmr; Resolution: No Resolution Dat Å
• Function: Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre- mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre- mRNA. Represses the splicing of MAPT/Tau exon 10 (PubMed:15009664). Binds to polypyrimidine-rich controlling element (PCE) of CFTR and promotes exon skipping of CFTR exon 9, thereby antagonizing TIA1 and its role in exon inclusion of CFTR exon 9 (PubMed:14966131). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to a polypyrimidine tract flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). In case of infection by picornaviruses, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES- mediated translation (PubMed:21518806). .
• Uniprot ID: PTBP1_HUMAN
• Ensembl ID: ENSG00000011304
• HGNC ID: HGNC:9583

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.36E-03; Fold-change: 6.44E-02; Z-score: 2.87E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Central carbon metabolism in cancer; Activation; hsa05230
• Cell Pathway Regulation: Glutamatergic synapse; Activation; hsa04724
• In Vitro Model: CA3 cells; Liver; Homo sapiens (Human); N.A.
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Huh7 cells; Kidney; Homo sapiens (Human); CVCL_U442
• In Vitro Model: SNU-182 cells; Liver; Homo sapiens (Human); CVCL_0090
• In Vitro Model: SNU-878 cells; Liver; Homo sapiens (Human); CVCL_5102
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Consistently, PTBP1 promotes glutamine uptake and the glutamine metabolism key enzyme, glutaminase (GLS) expression. Bioinformatics analysis predicted that the 3'-UTR of GLS mRNA contained PTBP1 binding motifs which were further validated by RNA immunoprecipitation and RNA pull-down assays. PTBP1 associated with GLS 3'-UTR to stabilize GLS mRNA in HCC cells. Finally, we demonstrated that the PTBP1-promoted CDDP resistance of HCC cells was through modulating the GLS-glutamine metabolism axis.

References

• Ref 1: Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase. Open Med (Wars). 2023 Sep 12;18(1):20230756.