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Literature summary for 3.4.21.B2 extracted from

  • Hu, D.; Liu, S.; Shi, L.; Li, C.; Wu, L.; Fan, Z.
    Cleavage of survivin by Granzyme M triggers degradation of the survivin-X-linked inhibitor of apoptosis protein (XIAP) complex to free caspase activity leading to cytolysis of target tumor cells (2010), J. Biol. Chem., 285, 18326-18335.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
additional information survivin silencing promotes X-linked inhibitor of apoptosis protein degradation and enhances GzmM-induced caspase activation as well as GzmM- and natural killer cell-induced cytolysis of target tumor cells Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
D86N-GzmM cDNA inserted into the Gal4 DNA binding domain vector. pGBKT7-D86N-GzmM and pGADT7-survivin cotransformed into the yeast stain AH109. Active GzmM and inactive D86N-GzmM mutant expressed in Escherichia coli Rosetta (DE3) strain. Stable HeLa transfectants or Jurkat cells incubated with different concentrations of GzmM or mutant D86N-GzmM Homo sapiens

Protein Variants

Protein Variants Comment Organism
D86N inactive, interaction between the mutant and survivin Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information noncleavable L138A survivin overexpression can significantly inhibit GzmM-mediated X-linked inhibitor of apoptosis protein degradation, caspase activation, and GzmM- and natural killer cell-induced cytotoxicity Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P51124
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-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
survivin + H2O the inhibitor of the apoptosis gene family member survivin is a physiological substrate for GzmM. GzmM hydrolyzes survivin at Leu-138 to remove the last four C-terminal residues. The truncated form is more rapidly hydrolyzed through proteasome-mediated degradation Homo sapiens ?
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?

Synonyms

Synonyms Comment Organism
Granzyme M
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Homo sapiens
GZmM
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Homo sapiens

General Information

General Information Comment Organism
physiological function GzmM associates with survivin. Survivin cleavage by GzmM abolishes the stability of the survivin-X-linked inhibitor of apoptosis protein complex and enhances X-linked inhibitor of apoptosis protein hydrolysis, which amplifies caspase-9 and 3 activation of target tumor cells Homo sapiens