Molecule Information

General Information of the Molecule (ID: Mol00266)

• Name: Caspase-1 (CASP1) ,Homo sapiens
• Synonyms: CASP-1; Interleukin-1 beta convertase; IL-1BC; Interleukin-1 beta-converting enzyme; ICE; IL-1 beta-converting enzyme; p45; IL1BC; IL1BCE
• Molecule Type: Protein
• Gene Name: CASP1
• Gene ID: 834
• Location: chr11:105025397-105035250[-]
• Sequence:
  MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDS
  VIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDN
  PAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRT
  GAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIR
  EGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVG
  VSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEY
  ACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH
• Function: Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides. Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes. Cleaves a tetrapeptide after an Asp residue at position P1. Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD. In contrast to cleavage of interleukins IL1B and IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part. Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive. In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly.
• Uniprot ID: CASP1_HUMAN
• Ensembl ID: ENSG00000137752
• HGNC ID: HGNC:1499

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

Gefitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung adenocarcinoma [1]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Gefitinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: miR377/CASP1 signaling pathway; Regulation; hsa05206
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment; Overexpression of SNHG5 suppressed the expression of miR-377; Overexpression of miR-377 suppressed the expression of CASP1 in PC9 cells; knockdown of CASP1 in SNHG5-overexpressed PC9GR cells abolished their gefitinib resistance.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung adenocarcinoma [1]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Sensitive Drug: Gefitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: miR377/CASP1 signaling pathway; Regulation; hsa05206
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment; Overexpression of SNHG5 suppressed the expression of miR-377; Overexpression of miR-377 suppressed the expression of CASP1 in PC9 cells; knockdown of CASP1 in SNHG5-overexpressed PC9GR cells abolished their gefitinib resistance.

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: 6.09E-84; Fold-change: -9.64E-01; Z-score: -2.21E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 7.93E-30; Fold-change: -7.60E-01; Z-score: -1.30E+00

References

• Ref 1: The long non-coding RNA SNHG5 regulates gefitinib resistance in lung adenocarcinoma cells by targetting miR-377/CASP1 axis. Biosci Rep. 2018 Aug 29;38(4):BSR20180400. doi: 10.1042/BSR20180400. Print 2018 Aug 31.