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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
is a
pro-apoptotic member of the
Bcl-2 gene family which is involved in initiating
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. 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
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 ...
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 membran ...
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.
Mechanism of action
Bax/
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 PIP
3), it forms the BAD-(
14-3-3) protein heterodimer. This leaves
Bcl-2 free to inhibit
Bax-triggered apoptosis. BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca
2+-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 block ...
) 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 with:
*
BCL2L1
*
BCL2A1[
* BCL2L2][
* MCL1][
* S100A10][
* YWHAQ]
See also
*Programmed cell death
Programmed cell death (PCD) sometimes referred to as cell, or cellular suicide is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usual ...
References
Further reading
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External links
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{{DEFAULTSORT:Bcl-2-Associated Death Promoter
Programmed cell death
Proteins