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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''BCL2L2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
on
chromosome 14
Chromosome 14 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 14 spans about 107 million base pairs (the building material of DNA) and represents between 3 and 3.5% of the total DNA ...
(
band
Band or BAND may refer to:
Places
*Bánd, a village in Hungary
*Band, Iran, a village in Urmia County, West Azerbaijan Province, Iran
*Band, Mureș, a commune in Romania
* Band-e Majid Khan, a village in Bukan County, West Azerbaijan Province, I ...
q11.2-q12).
It was originally discovered by Leonie Gibson,
Suzanne Cory
Suzanne Cory (born 11 March 1942) is an Australian molecular biologist. She has worked on the genetics of the immune system and cancer and has lobbied her country to invest in science. She is married to fellow scientist Jerry Adams, also a WE ...
and colleagues at the
Walter and Eliza Hall Institute of Medical Research
WEHI (), previously known as the Walter and Eliza Hall Institute of Medical Research, and as the Walter and Eliza Hall Institute, is Australia's oldest medical research institute. Sir Frank Macfarlane Burnet, who won the Nobel Prize in 1960 for ...
, who called it Bcl-w.
Function
This gene encodes a pro-survival (anti-
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 includ ...
) 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 an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating cells ...
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 testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...
.
Clinical significance
High levels of Bcl-w are seen in many cancers, including
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
,
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
,
non-small-cell lung carcinoma
Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...
, and
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
.
Breast cancer patients with
metastasis
Metastasis is a pathogenic agent's spread 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, then, ...
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 cancers develop at their primary site but then go on to metastasize or spread to other parts of the body. These fur ...
.
Elevated levels of Bcl-w has been shown to protect
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s from cell death induced by
amyloid beta
Amyloid beta (Aβ or Abeta) 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 precursor protein (APP), which is ...
.
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
patients with a mutant
PARK2
Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the ''PARK2'' gene. Parkin plays a critical role in ubiquitination – the process whereby molecules are covalently labelled with ubiquitin (Ub ...
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 approxi ...
.
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 a ...
has been shown to inhibit the
PI3K/AKT pathway leading to
downregulation
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary proc ...
of Bcl-w.
Interactions
BCL2L2 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:
*
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.
Function
The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family ...
*
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 troll ...
,
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). PP ...
.
References
Further reading
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External links
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{{Gene-14-stub