Molecule Information

General Information of the Molecule (ID: Mol00332)

• Name: Dual specificity protein phosphatase 1 (DUSP1) ,Homo sapiens
• Synonyms: Dual specificity protein phosphatase hVH1; Mitogen-activated protein kinase phosphatase 1; MAP kinase phosphatase 1; MKP-1; Protein-tyrosine phosphatase CL100; CL100; MKP1; PTPN10; VH1
• Molecule Type: Protein
• Gene Name: DUSP1
• Gene ID: 1843
• Location: chr5:172768096-172771195[-]
• Sequence:
  MVMEVGTLDAGGLRALLGERAAQCLLLDCRSFFAFNAGHIAGSVNVRFSTIVRRRAKGAM
  GLEHIVPNAELRGRLLAGAYHAVVLLDERSAALDGAKRDGTLALAAGALCREARAAQVFF
  LKGGYEAFSASCPELCSKQSTPMGLSLPLSTSVPDSAESGCSSCSTPLYDQGGPVEILPF
  LYLGSAYHASRKDMLDALGITALINVSANCPNHFEGHYQYKSIPVEDNHKADISSWFNEA
  IDFIDSIKNAGGRVFVHCQAGISRSATICLAYLMRTNRVKLDEAFEFVKQRRSIISPNFS
  FMGQLLQFESQVLAPHCSAEAGSPAMAVLDRGTSTTTVFNFPVSIPVHSTNSALSYLQSP
  ITTSPSC
• Function: Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle.
• Uniprot ID: DUS1_HUMAN
• Ensembl ID: ENSG00000120129
• HGNC ID: HGNC:3064

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

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [1]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: In non-small cell lung cancer (NSCLC) cells and xenografts, MkP-1 knockdown triggered the down-regulation of the metabolic enzymes and cytoprotective proteins, which are the target genes of Nrf2. Consequently, the cell growth was markedly inhibited with decrease of tumor metabolisms and GSH contents. Moreover, MkP-1 silencing sensitized NSCLC cells to cisplatin treatment. Mechanistically, MkP-1 inhibited the ubiquitylation of Nrf2 via a direct interaction with the transcription factor. Thus, MkP-1 and Nrf2 form a forward feedback loop in lung cancer cells, which stabilizing and activating Nrf2 to promote anabolic metabolism and GSH biosynthesis.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.60E-50; Fold-change: -2.35E+00; Z-score: -1.86E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 8.95E-21; Fold-change: -2.29E+00; Z-score: -1.45E+00

References

• Ref 1: Interplay of MKP-1 and Nrf2 drives tumor growth and drug resistance in non-small cell lung cancer. Aging (Albany NY). 2019 Dec 6;11(23):11329-11346. doi: 10.18632/aging.102531. Epub 2019 Dec 6.