Molecule Information

General Information of the Molecule (ID: Mol00175)

• Name: Tumor protein p53-inducible nuclear protein 1 (TP53INP1) ,Homo sapiens
• Synonyms: Stress-induced protein; p53-dependent damage-inducible nuclear protein 1; p53DINP1; P53DINP1; SIP
• Molecule Type: Protein
• Gene Name: TP53INP1
• Gene ID: 94241
• Location: chr8:94925972-94949378[-]
• Sequence:
  MFQRLNKMFVGEVSSSSNQEPEFNEKEDDEWILVDFIDTCTGFSAEEEEEEEDISEESPT
  EHPSVFSCLPASLECLADTSDSCFLQFESCPMEESWFITPPPCFTAGGLTTIKVETSPME
  NLLIEHPSMSVYAVHNSCPGLSEATRGTDELHSPSSPRVEAQNEMGQHIHCYVAALAAHT
  TFLEQPKSFRPSQWIKEHSERQPLNRNSLRRQNLTRDCHPRQVKHNGWVVHQPCPRQYNY
• Function: Antiproliferative and proapoptotic protein involved in cell stress response which acts as a dual regulator of transcription and autophagy. Acts as a positive regulator of autophagy. In response to cellular stress or activation of autophagy, relocates to autophagosomes where it interacts with autophagosome-associated proteins GABARAP, GABARAPL1/L2, MAP1LC3A/B/C and regulates autophagy. Acts as an antioxidant and plays a major role in p53/TP53-driven oxidative stress response. Possesses both a p53/TP53-independent intracellular reactive oxygen species (ROS) regulatory function and a p53/TP53-dependent transcription regulatory function. Positively regulates p53/TP53 and p73/TP73 and stimulates their capacity to induce apoptosis and regulate cell cycle. In response to double-strand DNA breaks, promotes p53/TP53 phosphorylation on 'Ser-46' and subsequent apoptosis. Acts as a tumor suppressor by inducing cell death by an autophagy and caspase-dependent mechanism. Can reduce cell migration by regulating the expression of SPARC.
• Uniprot ID: T53I1_HUMAN
• Ensembl ID: ENSG00000164938
• HGNC ID: HGNC:18022

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

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [1]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR182/TP53INP1 signaling pathway; Regulation; hsa05206
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-182 levels are significantly increased in HCC patients treated with cisplatin-based chemotherapy. Upregulated miR-182 inhibits TP53INP1 expression, which results in sequent cisplatin resistance.

Gemcitabine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [2]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: p73-mediated apoptosis signaling pathway; Inhibition; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: BT-549; Breast; Homo sapiens (Human); CVCL_1092
• In Vitro Model: MCF-10A; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: ZR-75-30 cells; Breast; Homo sapiens (Human); CVCL_1661
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: TUNEL assays
• Mechanism Description: microRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer Inhibition of miR200a enhances gemcitabine chemosensitivity in resistance cancer cells. TP53INP1 and YAP1 are involved in the RNA damage-induced p73-mediated apoptosis.

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Gastric cancer [3]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosomal delivery of miR 155 5p may induce EMT and chemoresistant phenotypes from paclitaxel resistant gastric cancer cells to the sensitive cells, which may be mediated by GATA3 and TP53INP1 suppression.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.90E-01; Fold-change: -4.33E-01; Z-score: -9.50E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 7.89E-01; Fold-change: 2.82E-03; Z-score: 6.27E-03

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.59E-05; Fold-change: -5.04E-01; Z-score: -9.56E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 8.35E-01; Fold-change: -8.89E-02; Z-score: -2.25E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 8.31E-01; Fold-change: -1.12E-01; Z-score: -9.41E-01

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.38E-01; Fold-change: -8.93E-02; Z-score: -1.90E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.85E-02; Fold-change: -1.81E-01; Z-score: -4.66E-01

References

• Ref 1: Upregulated miR-182 increases drug resistance in cisplatin-treated HCC cell by regulating TP53INP1. Gene. 2014 Apr 1;538(2):342-7. doi: 10.1016/j.gene.2013.12.043. Epub 2014 Jan 19.
• Ref 2: MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer. BMC Cancer. 2018 Jan 12;18(1):74. doi: 10.1186/s12885-017-3930-0.
• Ref 3: Paclitaxel resistant gastric cancer MGC 803 cells promote epithelial to mesenchymal transition and chemoresistance in paclitaxel sensitive cells via exosomal delivery of miR 155 5p. Int J Oncol. 2019 Jan;54(1):326-338. doi: 10.3892/ijo.2018.4601. Epub 2018 Oct 22.