Apoptosis regulatory
genes
,Apoptosis regulation pathways
• There are two main
for the induction and r
of apoptosis in
intracellular, which
mitochondria, and ext
which begins with the
of receptors on the cel
• They can occur
independently and tog
• The process of apop
be conditionally divi
three phases:
(inductive), effecto
degradation (de
phase).
,APAF1
• Apoptotic peptidase activating factor 1 is encoded by the gene
same name, located in humans on the short arm of chromosome
length of the polypeptide chain of the protein is 1,248 amino acids.
Expression is increased by the presence
• This gene encodes a cytoplasmic protein that initiates apoptos
of E2F and p53/TP53 factors, and protein contains multiple copies of the WD-40 domain, a c
decreased by HNRPA1, which binds to recruitment domain (CARD), and an ATPase domain (NB-ARC)
binding cytochrome c and dATP, this protein forms an olig
APAF1 mRNA. apoptosome. The apoptosome binds and cleaves the prepro
caspase-9, releasing its mature, activated form. Activated cas
Low levels of expression lead to neural stimulates the subsequent caspase cascade, which forces the
tube defects. undergo apoptosis. Alternative splicing results in several
transcripts encoding different isoforms.
,BCL2
• BCL2 (B-cell lymphoma protein 2,
apoptosis regulator) is a protein
encoded by the gene of the same
name, located in humans on the short
arm of chromosome 18.
• Inhibits apoptosis in many cell systems,
including lymphohematopoietic and
neuronal cells. Regulates cell death by
controlling mitochondrial membrane
permeability. Inhibits caspases by
preventing cytochrome c release from
mitochondria and/or by binding to the
apoptosis-activating factor APAF1. Also
acts as an inhibitor of autophagy:
interacts with BECN1 and AMBRA1 and
inhibits their autophagy function.
The highest levels of expression are
observed in T lymphocytes, NK cells, ovaries.
BCL2 is well established as a therapeutic
target due to its important role in apoptosis
and has a number of pharmaceutical
initiatives in cancer treatment.
, CASP9 Without proper function, abnormal tissue development
can occur, leading to abnormal function, disease, and
premature death. Loss-of-function mutations in caspase-9
are associated with immunodeficiencies, neural tube
defects, and increased gene expression is implicated in
the progression of amyotrophic lateral sclerosis, retina
detachment, and slow channel syndrome, as well as
various other neurological, autoimmune, and
cardiovascular disorders.
• The CASP9 gene encodes a
homonymous protein that acts as
an initiating caspase in the
intrinsic apoptosis pathway. Its
inactive form, ProC9, consists of
three distinct regions: an N-
terminal caspase recruitment
domain (CARD), a large catalytic
subunit, and a small catalytic
subunit. The active form of this
protein must remain attached to
the apoptosome to maintain its
catalytic activity.
genes
,Apoptosis regulation pathways
• There are two main
for the induction and r
of apoptosis in
intracellular, which
mitochondria, and ext
which begins with the
of receptors on the cel
• They can occur
independently and tog
• The process of apop
be conditionally divi
three phases:
(inductive), effecto
degradation (de
phase).
,APAF1
• Apoptotic peptidase activating factor 1 is encoded by the gene
same name, located in humans on the short arm of chromosome
length of the polypeptide chain of the protein is 1,248 amino acids.
Expression is increased by the presence
• This gene encodes a cytoplasmic protein that initiates apoptos
of E2F and p53/TP53 factors, and protein contains multiple copies of the WD-40 domain, a c
decreased by HNRPA1, which binds to recruitment domain (CARD), and an ATPase domain (NB-ARC)
binding cytochrome c and dATP, this protein forms an olig
APAF1 mRNA. apoptosome. The apoptosome binds and cleaves the prepro
caspase-9, releasing its mature, activated form. Activated cas
Low levels of expression lead to neural stimulates the subsequent caspase cascade, which forces the
tube defects. undergo apoptosis. Alternative splicing results in several
transcripts encoding different isoforms.
,BCL2
• BCL2 (B-cell lymphoma protein 2,
apoptosis regulator) is a protein
encoded by the gene of the same
name, located in humans on the short
arm of chromosome 18.
• Inhibits apoptosis in many cell systems,
including lymphohematopoietic and
neuronal cells. Regulates cell death by
controlling mitochondrial membrane
permeability. Inhibits caspases by
preventing cytochrome c release from
mitochondria and/or by binding to the
apoptosis-activating factor APAF1. Also
acts as an inhibitor of autophagy:
interacts with BECN1 and AMBRA1 and
inhibits their autophagy function.
The highest levels of expression are
observed in T lymphocytes, NK cells, ovaries.
BCL2 is well established as a therapeutic
target due to its important role in apoptosis
and has a number of pharmaceutical
initiatives in cancer treatment.
, CASP9 Without proper function, abnormal tissue development
can occur, leading to abnormal function, disease, and
premature death. Loss-of-function mutations in caspase-9
are associated with immunodeficiencies, neural tube
defects, and increased gene expression is implicated in
the progression of amyotrophic lateral sclerosis, retina
detachment, and slow channel syndrome, as well as
various other neurological, autoimmune, and
cardiovascular disorders.
• The CASP9 gene encodes a
homonymous protein that acts as
an initiating caspase in the
intrinsic apoptosis pathway. Its
inactive form, ProC9, consists of
three distinct regions: an N-
terminal caspase recruitment
domain (CARD), a large catalytic
subunit, and a small catalytic
subunit. The active form of this
protein must remain attached to
the apoptosome to maintain its
catalytic activity.
