The BCL2 associated agonist of cell death (BAD)

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

is a

pro-apoptotic Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

member of the

Bcl-2 Bcl-2 (B-cell lymphoma 2), encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosis. ...

gene family which is involved in initiating

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. BAD is a member of the BH3-only family, a subfamily of the

Bcl-2 family The Bcl-2 familyTC# 1.A.21 consists of a number of evolutionarily-conserved proteins that share Bcl-2 homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion. ...

. It does not contain a

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

transmembrane

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

for outer

mitochondrial membrane A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used t ...

and

nuclear envelope The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membrane ...

targeting, unlike most other members of the

. After activation, it is able to form a

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

with anti-apoptotic proteins and prevent them from stopping apoptosis.

Mechanism of action

Bax/ Bak are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows

cytochrome c The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...

to escape into the cytoplasm and activate the pro-apoptotic caspase cascade. The anti-apoptotic

and

Bcl-xL B-cell lymphoma-extra large (Bcl-xL), encoded by the BCL2-like 1 gene, is a transmembrane molecule in the mitochondria. It is a member of the Bcl-2 family of proteins, and acts as an anti-apoptotic protein by preventing the release of mitochondr ...

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

and

, 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 heterodimer. This leaves

free to inhibit Bax-triggered apoptosis. BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca²⁺-stimulated

Calcineurin Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be bloc ...

) is pro-apoptotic. The latter may be involved in neural diseases such as schizophrenia.Foster, T.C. et al. (2001) J. Neurosci. 21, 4066-4073, "Calcineurin Links Ca++ Dysregulation with Brain Aging"(

Interactions

Bcl-2-associated death promoter has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

BCL2L1 Bcl-2-like protein 1 is a protein encoded in humans by the ''BCL2L1'' gene. Through alternative splicing, the gene encodes both of the human proteins Bcl-xL and Bcl-xS. Function The protein encoded by this gene belongs to the Bcl-2 protein ...

* BCL2A1 *

BCL2L2 Bcl-2-like protein 2 is a 193-amino acid protein that in humans is encoded by the ''BCL2L2'' gene on chromosome 14 ( band q11.2-q12). It was originally discovered by Leonie Gibson, Suzanne Cory and colleagues at the Walter and Eliza Hall Instit ...

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 tr ...

S100A10 S100 calcium-binding protein A10 (S100A10), also known as p11, is a protein that is encoded by the ''S100A10'' gene in humans and the ''S100a10'' gene in other species. S100A10 is a member of the S100 family of proteins containing two EF-hand cal ...

YWHAQ 14-3-3 protein theta is a protein that in humans is encoded by the ''YWHAQ'' gene. Function This gene product belongs to the 14-3-3 family of proteins that mediate signal transduction by binding to phosphoserine-containing proteins. This highl ...

and *

YWHAZ 14-3-3 protein zeta/delta (14-3-3ζ) is a protein that in humans is encoded by the ''YWHAZ'' gene on chromosome 8. The protein encoded by this gene is a member of the 14-3-3 protein family and a central hub protein for many signal transduction pat ...

References

External links

* * {{DEFAULTSORT:Bcl-2-Associated Death Promoter Programmed cell death Proteins

Mechanism of action

Interactions

See also

References

Further reading

External links