Bcl-2-like protein 2 is a 193-amino acid
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 ...
that in humans is encoded by the ''BCL2L2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
on
chromosome 14 (
band q11.2-q12).
It was originally discovered by Leonie Gibson,
Suzanne Cory and colleagues at the
Walter and Eliza Hall Institute of Medical Research
Walter may refer to:
People and fictional characters
* Walter (name), including a list of people and fictional and mythical characters with the given name or surname
* Little Walter, American blues harmonica player Marion Walter Jacobs (1930–1 ...
, who called it Bcl-w.
Function
This gene encodes a pro-survival (anti-
apoptotic
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes ( morphology) and death. These ...
) member of the
bcl-2 protein family, and is most similar to
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 ...
.
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 to contribute to reduced cell apoptosis under
cytotoxic
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...
conditions. Studies of the related gene in mice indicated a role in the survival of
NGF- and
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...
-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...
.
Clinical significance
High levels of Bcl-w are seen in many cancers, including
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...
,
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
,
non-small-cell lung carcinoma
Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...
, and
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
.
Breast cancer patients with
metastasis
Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
have higher Bcl-w than breast cancer patients only having
primary tumor
A primary tumor is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass. Most solid cancers develop at their primary site but may then go on to metastasize or spread to other parts of the b ...
.
Elevated levels of Bcl-w has been shown to protect
neuron
A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
s from cell death induced by
amyloid beta
Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...
.
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
patients with a mutant
PARK2 gene have elevated Bcl-w.
Bcl-w has been shown to contribute to
cellular senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of appro ...
.
Quercetin
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor ...
has been shown to inhibit the
PI3K/AKT pathway leading to
downregulation
In biochemistry, in the biology, biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell (biology), cell decreases the production and quantities of its cellular ...
of Bcl-w.
Interactions
BCL2L2 has been shown to
interact with:
*
BCL2L11
Bcl-2-like protein 11, commonly called BIM (Bcl-2 Interacting Mediator of cell death), is a protein that in humans is encoded by the ''BCL2L11'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredit ...
*
BAD
Bad or BAD may refer to:
Common meanings
*Evil, the opposite of moral good
* Erroneous, inaccurate or incorrect
* Unhealthy, or counter to well-being
*Antagonist, the threat or obstacle of moral good
Acronyms
* BAD-2, a Soviet armored trolley ...
,
PPP1CA
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit is an enzyme that in humans is encoded by the ''PPP1CA'' gene.
Function
The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). P ...
.
References
Further reading
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External links
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{{PDB Gallery, geneid=599