Caspase-9

Developmental stage

Expressed at low levels in fetal heart, at moderate levels in neonate heart, and at high levels in adult heart.

Function

Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).

Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9.

Post-translational modifications

Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events.

Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at Thr-125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation. Phosphorylation on Tyr-153 by ABL1/c-Abl; occurs in the response of cells to DNA damage.

Sequence similarities

Belongs to the peptidase C14A family.

Tissue specificity

Ubiquitous, with highest expression in the heart, moderate expression in liver, skeletal muscle, and pancreas. Low levels in all other tissues. Within the heart, specifically expressed in myocytes.

Alternative names

• Caspase-9
• CASP-9
• Apoptotic protease Mch-6
• Apoptotic protease-activating factor 3
• ICE-like apoptotic protease 6
• APAF-3
• ICE-LAP6
• CASP9
• MCH6

Database links

• entrezGene:842
• omim:602234
• swissprot:P55211

Target type

Proteins

Primary research area

Oncology

Molecular weight

46281Da