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Literature summary for 3.4.21.B2 extracted from

  • de Poot, S.A.; Lai, K.W.; van der Wal, L.; Plasman, K.; Van Damme, P.; Porter, A.C.; Gevaert, K.; Bovenschen, N.
    Granzyme M targets topoisomerase II alpha to trigger cell cycle arrest and caspase-dependent apoptosis (2014), Cell Death Differ., 21, 416-426.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.21.B2

Cloned(Commentary)

Cloned (Comment) Organism
expression in Pichia pastoris Homo sapiens

Protein Variants

Protein Variants Comment Organism
S195A inactive Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P51124
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
topoisomerase II alpha + H2O
-
 Homo sapiens ? cleavage of topoisomerase II alpha by granzyme M at Leu1280 separates topoisomerase II alpha functional domains from the nuclear localization signals and leads to nuclear exit of topoisomerase II alpha catalytic activity ?

General Information

General Information Comment Organism
physiological function granzyme M induced cell death is largely caspase-dependent with various hallmarks of classical apoptosis, coinciding with caspase-independent G2/M cell cycle arrest. The nuclear enzyme topoisomerase II alpha is a physiological substrate of granzyme M. Cleavage of topoisomerase II alpha by granzyme M at Leu1280 separates topoisomerase II alpha functional domains from the nuclear localization signals, leading to nuclear exit of topoisomerase II alpha catalytic activity, thereby rendering it nonfunctional. Similar to the apoptotic phenotype of granzyme M, topoisomerase II alpha depletion in tumor cells leads to cell cycle arrest in G2/M, mitochondrial perturbations, caspase activation, and apoptosis Homo sapiens