3.4.22.62: caspase-9
This is an abbreviated version!
For detailed information about caspase-9, go to the full flat file.
Word Map on EC 3.4.22.62
-
3.4.22.62
-
caspase-3
-
bcl-2
-
parp
-
anti-apoptotic
-
pro-apoptotic
-
tunel
-
necrosis
-
apoptosis-related
-
caspase-dependent
-
apoptosis-inducing
-
jnk
-
apaf-1
-
annexin
-
extrinsic
-
cyclin
-
leukemia
-
bid
-
neuroprotective
-
depolarization
-
polyadp-ribose
-
survivin
-
hoechst
-
z-vad-fmk
-
antiproliferative
-
adp-ribose
-
xiap
-
iodide
-
deoxynucleotidyl
-
mitochondria-dependent
-
mitochondria-mediated
-
cisplatin
-
dutp
-
fadd
-
procaspase-3
-
caspase-mediated
-
pan-caspase
-
fas-mediated
-
trail
-
fas-associated
-
trail-induced
-
bcl-2-associated
-
apoptogenic
-
pharmacology
-
cdc25c
-
puma
-
transferase-mediated
-
executioner
-
factor-related
-
deltapsim
-
medicine
-
tunel-positive
-
sub-g1
- 3.4.22.62
- caspase-3
- bcl-2
- parp
-
anti-apoptotic
-
pro-apoptotic
-
tunel
- necrosis
-
apoptosis-related
-
caspase-dependent
-
apoptosis-inducing
- jnk
- apaf-1
-
annexin
-
extrinsic
- cyclin
- leukemia
- bid
-
neuroprotective
-
depolarization
-
polyadp-ribose
- survivin
-
hoechst
- z-vad-fmk
-
antiproliferative
- adp-ribose
- xiap
- iodide
-
deoxynucleotidyl
-
mitochondria-dependent
-
mitochondria-mediated
- cisplatin
- dutp
- fadd
- procaspase-3
-
caspase-mediated
-
pan-caspase
-
fas-mediated
-
trail
-
fas-associated
-
trail-induced
-
bcl-2-associated
-
apoptogenic
- pharmacology
- cdc25c
- puma
-
transferase-mediated
-
executioner
-
factor-related
-
deltapsim
- medicine
-
tunel-positive
-
sub-g1
Reaction
strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-Asp-/-Xaa =
Synonyms
APAF, Apaf-3, apoptotic protease activating factor 3, apoptotic protease Mch-6, C14.010, CASP-9, casp9, casp9-gamma, caspase 9, caspase-9, ICE-LAP6, ICE-like apoptotic protease 6, Mch6
ECTree
Advanced search results
General Information
General Information on EC 3.4.22.62 - caspase-9
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
evolution
malfunction
metabolism
physiological function
additional information
-
multiple sequence alignment and phylogenetic tree show that fish and human caspase 9 are highly evolutionarily conserved
evolution
-
key structural and catalytic features are conserved across the entire family of cysteine-dependent aspartate-specific proteases (caspases)
evolution
-
members of the caspase family can be subdivided into initiator and effector caspases depending on their placement within the cascade of apoptosis signal transduction. Initiator caspases comprise caspase-2, -8, -9 and -10, which are capable of activating downstream caspases (executioners) after cleavage either directly through proteolysis or indirectly via a secondary messenger mechanism
-
inhibition of caspase-9 activity results in unexpected, marked enhancement of cell death, inhibition of caspase-9 blocks the autophagic process by modulating lysosomal pH and acid-dependent cathepsin activities and augments cell death due to blockage of cytoprotective autophagy. Knockdown of caspase-9 expression by specific siRNA causes increased susceptibility to NSAID FR122047-induced cell death
malfunction
-
caspase-9 inactivation by specific siRNA restrains the cleavage of Bcl-2 and Bcl-xL, inhibition of caspase-9 also prevents the degradation of Bcl-2 and Bcl-xL
malfunction
-
introduction of a dominant negative Casp9 inhibits mitochondrial remodeling without affecting the release of cytochrome c
malfunction
-
loss of caspase-9 results in increased DNA damage and mutation burden after exposure to alkylating agents. Casp9 deficiency results in decreased erythroid and B-cell progenitor abundance and impaired function of hematopoietic stem cells after transplantation. Loss of Casp9 alters hematopoietic progenitor cell frequency
malfunction
-
loss of caspase-9 results in increased DNA damage and mutation burden after exposure to alkylating agents. Casp9 deficiency results in decreased erythroid and B-cell progenitor abundance and impaired function of hematopoietic stem cells after transplantation. Loss of Casp9 alters hematopoietic progenitor cell frequency
-
-
p53 mediates DNA damaging drug-induced apoptosis in IMR32 cells through the caspase-9 pathway, molecular pathway, overview
metabolism
-
activation of caspase-9 and caspase-3 via proteolytic cleavage is crucial for the regulation of the apoptotic program
metabolism
-
caspase-9 regulates Puma and caspase-3 activation in apoptosis in cancer cells
metabolism
-
caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis, which is is a form of programmed cell death that is regulated by the Bcl-2 family and caspase family of proteins. The caspase cascade is responsible for executing cell death following cytochrome c release. Caspase-9 is required for mitochondrial morphological changes and reactive oxygen species production by cleaving and activating Bid into tBid. After activation by caspase-9, caspase-3 inhibits reactive oxygen species production and is required for efficient execution of apoptosis, while effector caspase-7 is required for apoptotic cell detachment
metabolism
-
of the caspases involved in apoptosis signal transduction, the initiator caspases-2, -8 and -9 are activated at multi-protein activation platforms, and activation is thought to involve homo-dimerisation of the monomeric zymogens. Modeling of caspase-9 signalling dynamics on the apoptosome, overview
-
activation of caspase-9 requires mitochondrial release of cytochrome c to the cytoplasm during apoptosis
physiological function
-
caspase-9 is initiator in the mitochondrial pathway. Cyt-c and dATP bind in the cytoplasm to an adaptor protein named Apaf-1 and promote formation of the multi-protein apoptosome complex that binds the pro-casp-9. Consequently pro-casp-9 oligomerizes within this complex and is activated by it own autocleavage. In addition to its function as initiator of the mitochondrial apoptotic cascade, caspase-9 can acts also as an executer which among other non-apoptotic functions it forms an Sp1-p53 complex that activates the long terminal repeats by binding to an Sp1 recognition site residing in the long terminal repeats. Ectopic casp-9 but not ectopic casp-3 activates the LTR expression and induces the Sp1-p53 complex formation and its binding to the ERR-1 oligonucleotide
physiological function
-
caspase-9 mediates activation of the mitochondrial death pathway, induced by trichothecin and leading to apoptosis of HepG2 cells with diminished expression of antiapoptotic protein Bcl-2 and enhanced expression of proapoptotic protein Bax at mRNA levels, molecular mechanism, overview. The decrement of mitochondrial function results from the overloaded calcium and ROS production
physiological function
-
involvement of caspase-9 in autophagy-mediated cell survival pathway
physiological function
-
caspase-9 induces feedback apoptosis of the mitochondrion by the cleavage of antiapoptotic Bcl-2 and Bcl-xL. Caspase-9 mediates Puma activation in protein kinase inhibitor 7-hydroxystaurosporine UCN-01-induced apoptosis, UCN-01 triggers Puma-induced mitochondrial apoptosis pathway, p53-independent Puma induction is pivotal for the anticancer effects of UCN-01. Caspase-9 enhances Puma activation by cleaving Bcl-2 and Bcl-xL independent of caspase-3. Caspase-9 also directly activates caspase-3 and apoptosis
physiological function
-
caspase-9 is an upstream or initiator caspase that is regulated differently from all other caspases, as interaction with natural inhibitor XIAP-BIR3 occurs at the dimer interface maintaining caspase-9 in an inactive monomeric state
physiological function
-
caspase-9 is required for mitochondrial morphological changes and reactive oxygen species production by cleaving and activating Bid into tBid, it activates caspase-3 and is necessary to remodel the mitochondria during intrinsic apoptosis
physiological function
-
caspase-9 is required for normal development of myeloid, lymphoid, and erythroid cells in mice. Role of caspase-9, the initiator caspase of the intrinsic apoptotic cascade, in murine fetal and adult hematopoiesis, overview
physiological function
-
caspase-9 is the essential initiator caspase required for apoptosis signalling through the mitochondrial pathway, dynamics of caspase-9 signalling on the apoptosome, detailed overview
physiological function
-
caspase-9 may play an essential role in Cd induced apoptosis
physiological function
-
caspase-9 mediates traumatic photoreceptor death, contribution of caspase-9 to photoreceptor death in commotio retinae, overview
physiological function
-
initiator caspases, such as caspase-9, function in recruitment and regulation and are designated as caspase activation and recruitment domains. As an initiator, caspase-9 regulates the upstream stages of the apoptotic caspase cascade, making it a critical control point. Inhibition by zinc has a regulatory function, and its relief is central to both small-molecule and natively induced caspase activation
physiological function
-
caspase-9 is required for normal development of myeloid, lymphoid, and erythroid cells in mice. Role of caspase-9, the initiator caspase of the intrinsic apoptotic cascade, in murine fetal and adult hematopoiesis, overview
-
-
during H2O2-induced apoptosis, caspase 3 is activated directly through caspase 8 and not through the mitochondria-dependent caspase 9 activation
additional information
-
the caspase family signature histidine active-site H236SQYDCCVVIMLSHG250, the cysteine active-site K290PKLFFIQACGG301 and the caspase 9 characteristic pentapeptide active-site QACGG are located in the p20 domain
additional information
-
treatment with the NSAID FR122047 promotes apoptosis and caspase activation in MCF-7 cells
additional information
-
modeling of the regulation of caspase-9 activation and activity that arise from the complexity of multi-protein interactions at the apoptosome