Table 1 Selected genes involved in the regulation of apoptosis

Tumor Protein 53 (TP53)

Transcriptionally regulates target genes that induce cell cycle

arrest, apoptosis, senescence, DNA repair, or changes in

metabolism in response to cellular stresses.

Tumor Necrosis Factor

(TNF)

Binds and functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR to regulate cell proliferation, differentiation,

and apoptosis.

PRKCQ

Protein kinase C family member; substrate for Caspase-3; phosphorylates BAD and required to activate NFκB (via CARD11 phosphorylation) and AP-1.

FAS & FAS Ligand (FASL)

Death domain-containing receptor, binding of FASL to FAS

allows the formation of a death-inducing signaling complex.

CASPASE (CASP)

Gene family involved in the execution of apoptosis. There are 2

classes of caspases, which include: initiators (e.g., CASP2, CASP8, CASP9, and CASP10) and effectors (e.g., CASP3, CASP6, CASP7). Initiator caspases activate pro-forms of effector caspases,

enabling effectors to trigger the apoptosis process.

CARD8 (Caspase

recruitment domain

family, member 8)

CARD family protein; involved in various pathways which

regulate caspases or NFκB; isoforms interact with caspases to

signal apoptosis.

BCL2-associated X (BAX)

Forms a heterodimer with BCL2 and functions as an apoptotic

activator involved mitochondrial release of cytochrome c.

BCL2-antagonist/killer 1

(BAK1)

Induces apoptosis by increasing cytochrome c release; interacts

with the TP53 after exposure to cell stress.

BCL2-associated agonist of

cell death (BAD)

Forms heterodimers with BCLXL and BCL2 to reverse their death repressor activity.

BCL2-like 10 (BCL2L10)

Interacts with BCL2 proteins (e.g., BCL2, BCL2L1/BCLXL, and

BAX).

BCL2-like 11 (BCL2L11)

(aka BIM); Interacts with other members of the BCL2 protein

family (e.g., BCL2, BCL2L1/BCLXL, and MCL1) to act as an

apoptosis activator.

BCL2-like 14 (BCL2L14)

Apoptosis facilitator; interacts with BCL2 family members; p53-

target gene.

BH3 interacting domain

death agonist (BID)

Induced by CASP8; CASP8 cleaves the protein encoded by this

gene, and the COOH-terminal part translocates to mitochondria,

which triggers cytochrome c release.

BCL2-interacting killer

(BIK)

Interacts with survival-promoting proteins to enhance

programmed cell death.

BCL2/adenovirus E1B

19 kDa interacting protein

3-like (BNIP3L)

(aka NIX); BCL2/adenovirus E1B 19 kd-interacting protein (BNIP)

gene that may function simultaneously with BNIP3 and play a

role in tumor suppression.

PRKCD

Translocates into nucleus during apoptosis. Nuclear PRKCD

regulates initiation of cytosolic apoptosis machinery, and

subsequent caspase activation and DNA fragmentation.

AKT3

Phosphorylate and inactivate BAD. Activates NFκB via IκB kinase regulation. Regulates cell signals in response to insulin and

growth factors.

B-cell CL/lymphoma 2 (BCL2)

Blocks the release of pro-apoptotic cytochrome c and caspase

activation.

NFκB

Inhibit caspases 3, 6, 7 stimulation via IAP (inhibitor of

apoptosis) activation.

PIK3CB

Interacts with growth factor receptors; activates AKT3; target

for PRKC.

RAF1

Inhibits BIM and BAD activation via ERK1/2 stimulation.

BCL2-related protein A1 (BCL2A1)

Reduces cytochrome c release from mitochondria and blocks

caspase activation.

Baculoviral IAP repeat-containing 2 (BIRC2)

(aka CIAP1); Inhibits apoptosis by binding to tumor necrosis

factor receptor-associated factors TRAF1 and TRAF2.

PRKCE

Blocks mitochondrial-dependent caspase activation;

phosphorylates and activates RAF-1; phosphorylates and

inactivates BAD; activates AKT via DNA-dependent protein kinase

(DNA-PK).

IKBKE

Induces BCL-2 expression via NFκB signaling and interaction.