Bcl-2-associated death promoter
Encyclopedia
The Bcl-2-associated death promoter (BAD) protein
is a pro-apoptotic
member of the Bcl-2
gene family which is involved in initiating apoptosis
. BAD is a member of the BH3-only family
, a subfamily of the Bcl-2 family
. It does not contain a C-terminal transmembrane domain
for outer mitochondrial membrane and nuclear envelope
targeting, unlike most other members of the Bcl-2 family
. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.
/Bak
are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows cytochrome c
to escape into the cytoplasm and activate the pro-apoptotic caspase cascade. The anti-apoptotic Bcl-2
and Bcl-xL
proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c.
Dephosphorylated BAD forms a heterodimer with Bcl-2
and Bcl-xL
, inactivating them and thus allowing Bax
/Bak
-triggered apoptosis. When BAD is phosphorylated by Akt/protein kinase B
(triggered by PIP3), it forms the BAD-(14-3-3)protein homodimer. This leaves Bcl-2
free to inhibit Bax
-triggered apoptosis. BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca2+-stimulated Calcineurin
) is pro-apoptotic. The latter may be involved in neural diseases such as schizophrenia.
Bcl-2-associated death promoter has been shown to interact
with BCL2-like 1
, BCL2L2
, Bcl-2
, BCL2-related protein A1, YWHAQ
, YWHAZ
, MCL1
and S100A10
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
is a pro-apoptotic
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
member of the Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
gene family which is involved in initiating apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. BAD is a member of the BH3-only family
, a subfamily of the Bcl-2 family
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
. It does not contain a C-terminal transmembrane domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
for outer mitochondrial membrane and nuclear envelope
Nuclear envelope
A nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...
targeting, unlike most other members of the Bcl-2 family
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.
Mechanism of Action
BaxBcl-2-associated X protein
The Bcl-2–associated X protein, or Bax is a protein of the Bcl-2 gene family. It promotes apoptosis by competing with Bcl-2 proper.The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family....
/Bak
Bcl-2 homologous antagonist killer
Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the BAK1 gene. BAK1 orthologs have been identified in most mammals for which complete genome data are available....
are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
to escape into the cytoplasm and activate the pro-apoptotic caspase cascade. The anti-apoptotic Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
and Bcl-xL
Bcl-xL
B-cell lymphoma-extra large is a transmembrane molecule in the mitochondria. It is involved in the signal transduction pathway of the FAS-L. It is one of several anti-apoptotic proteins which are members of the Bcl-2 family of proteins. It has been implicated in the survival of cancer cells. Other...
proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c.
Dephosphorylated BAD forms a heterodimer with Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
and Bcl-xL
Bcl-xL
B-cell lymphoma-extra large is a transmembrane molecule in the mitochondria. It is involved in the signal transduction pathway of the FAS-L. It is one of several anti-apoptotic proteins which are members of the Bcl-2 family of proteins. It has been implicated in the survival of cancer cells. Other...
, inactivating them and thus allowing Bax
Bcl-2-associated X protein
The Bcl-2–associated X protein, or Bax is a protein of the Bcl-2 gene family. It promotes apoptosis by competing with Bcl-2 proper.The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family....
/Bak
Bcl-2 homologous antagonist killer
Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the BAK1 gene. BAK1 orthologs have been identified in most mammals for which complete genome data are available....
-triggered apoptosis. When BAD is phosphorylated by Akt/protein kinase B
AKT
Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...
(triggered by PIP3), it forms the BAD-(14-3-3)protein homodimer. This leaves Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
free to inhibit Bax
Bcl-2-associated X protein
The Bcl-2–associated X protein, or Bax is a protein of the Bcl-2 gene family. It promotes apoptosis by competing with Bcl-2 proper.The BAX gene was the first identified pro-apoptotic member of the Bcl-2 protein family....
-triggered apoptosis. BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca2+-stimulated Calcineurin
Calcineurin
Calcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
) is pro-apoptotic. The latter may be involved in neural diseases such as schizophrenia.
Interactions
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with BCL2-like 1
BCL2-like 1 (gene)
Bcl-2-like protein 1 is a protein that in humans is encoded by the BCL2L1 gene.-Interactions:BCL2-like 1 has been shown to interact with RAD9A, RTN1, BAK1, Reticulon 4, Bcl-2-associated X protein, BCAP31, Bcl-2-interacting killer, PPP1CA, Noxa, VDAC1, BCL2L11, Bcl-2-associated death promoter,...
, BCL2L2
BCL2L2
Bcl-2-like protein 2 is a protein that in humans is encoded by the BCL2L2 gene.This gene encodes a pro-survival member of the bcl-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown...
, Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
, BCL2-related protein A1, YWHAQ
YWHAQ
14-3-3 protein theta is a protein that in humans is encoded by the YWHAQ gene.-Interactions:YWHAQ has been shown to interact with MEF2D, Bcl-2-associated X protein, CRTC2, C-Raf, Histone deacetylase 5, NRIP1, Protein kinase Mζ, UCP3, PFKFB2, Telomerase reverse transcriptase, Bcl-2-associated death...
, YWHAZ
YWHAZ
14-3-3 protein zeta/delta is a protein that in humans is encoded by the YWHAZ gene.-Interactions:YWHAZ has been shown to interact with TSC2, LIMK1, CDC25B, AKT1, BCAR1, Interleukin-9 receptor, C-Raf, HMGN1, Vimentin, Tau protein, Protein kinase Mζ, GP1BB, GP1BA, TNFAIP3, Bcl-2-associated death...
, MCL1
MCL1
Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the MCL1 gene.- Function :The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been...
and S100A10
S100A10
S100-A10, also known as p11, is a protein that is encoded by the S100A10 gene in humans and the S100a10 gene in other species. S100-A10 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide...
.