Bcl-2
Encyclopedia
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 translocation
s involving chromosome
s 14 and 18 in follicular lymphoma
s. Bcl-2 orthologs have been identified in numerous mammals for which complete genome data are available. The two isoforms of Bcl-2, Isoform 1, also known as 1G5M, and Isoform 2, also known as 1G5O/1GJH, exhibit similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, suggest differences in antiapoptotic activity for the two isoforms
s, including melanoma
, breast
, prostate
, and lung carcinomas
, as well as schizophrenia
and autoimmunity
. It is also thought to be involved in resistance to conventional cancer treatment. This suggests that decreased apoptosis may play a role in the development of cancer.
Cancer occurs when the homeostatic balance between cell growth and death is disturbed. Research in cancer biology has discovered that a variety of aberrations in gene expression of anti-apoptotic, pro-apoptotic and BH3-only proteins can contribute to the many forms of the disease. An example can be seen in lymphoma
s. The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone does not cause cancer. But simultaneous over-expression of Bcl-2 and the proto-oncogene myc
may produce aggressive B-cell malignancies including lymphoma.
In follicular lymphoma
, a chromosomal translocation
commonly occurs between the fourteenth and the eighteenth chromosome
s—t(14;18)—which places the Bcl-2 gene next to the immunoglobulin heavy chain locus. This fusion gene is deregulated, leading to the transcription of excessively high levels of Bcl-2. This decreases the propensity of these cells for undergoing apoptosis.
Apoptosis also plays a very active role in regulating the immune system. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the case of defective apoptosis, it may contribute to etiological aspects of autoimmune diseases. The autoimmune disease, type 1 diabetes can be caused by defective apoptosis, which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cell
s are the most important antigen presenting cells of the immune system, their activity must be tightly regulated by such mechanisms as apoptosis. Researchers have found that mice containing dendritic cells that are Bim
-/-, thus unable to induce effective apoptosis, obtain autoimmune diseases more so than those that have normal dendritic cells. Other studies have shown that the lifespan of dendritic cells may be partly controlled by a timer dependent on anti-apoptotic Bcl-2.
Apoptosis plays a very important role in regulating a variety of diseases that have enormous social impacts. For example, schizophrenia is a neurodegenerative disease that may result from an abnormal ratio of pro- and anti-apoptotic factors. There is some evidence that this defective apoptosis may result from abnormal expression of Bcl-2 and increased expression of caspase-3.
Further research into the family of Bcl-2 proteins will provide a more complete picture on how these proteins interact with each other to promote and inhibit apoptosis. An understanding of the mechanisms involved may help develop new therapies for treating cancer, autoimmune conditions, and neurological diseases.
to identify cells containing the antigen. In healthy tissue, these antibodies will react with B-cells in the mantle zone
, as well as some T-cells. However, there is a considerable increase in positive cells in follicular lymphoma
, as well as many other forms of cancer. In some cases, the presence or absence of Bcl-2 staining in biopsies
may be significant for the patient's prognosis
or likelihood of relapse
.
drug Genasense (G3139) has been developed by Genta Incorporated
to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed.
It was shown that the proliferation of human lymphoma
cells
(with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro
studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.
These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004
By the first quarter 2010, Genasense had not received FDA
approval due to disappointing results in a melanoma trial. Although safety and efficacy of Genasense have not been established for any use, Genta Incorporated still claims on its website that studies are currently underway to examine the potential role of Genasense in a variety of clinical indications.
described in the mid-2000s a novel inhibitor of Bcl-2, Bcl-xL and Bcl-w, known as ABT-737. ABT-737 is one among many so-called BH3 mimetic small molecule inhibitors (SMI) targeting Bcl-2 and Bcl-2-related proteins such as Bcl-xL and Bcl-w but not A1 and Mcl-1, which may prove valuable in the therapy of lymphoma and other blood cancers.
Bcl-2 has been shown to interact
with RAD9A
, BAK1, Reticulon 4
, Bcl-2-associated X protein
, Caspase 8
, BECN1
, SOD1
, Bcl-2-interacting killer
, BH3 interacting domain death agonist
, RRAS
, C-Raf
, BCL2L11
, BNIPL
, HRK
, PSEN1
, BMF
, BNIP2
, BNIP3
, Nerve Growth factor IB
, BCL2-like 1
, Myc
, BCAP31
, SMN1
, CAPN2
, PPP2CA
, Noxa
, Cdk1
, TP53BP2
, Bcl-2-associated death promoter
and IRS1
.
; BAK1; BAX
; BCL2; BCL2A1
; BCL2L1; BCL2L10
; BCL2L13
;
BCL2L14
; BCL2L2
; BCL2L7P1; BOK
; MCL1
; LGALS7 (Galectin-7)
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...
regulator proteins encoded by the BCL2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. 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 translocation
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
s involving chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s 14 and 18 in follicular lymphoma
Follicular lymphoma
Follicular lymphoma is the most common of the indolent non-Hodgkin's lymphomas, and the second most common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells , which has at least a partially follicular pattern...
s. Bcl-2 orthologs have been identified in numerous mammals for which complete genome data are available. The two isoforms of Bcl-2, Isoform 1, also known as 1G5M, and Isoform 2, also known as 1G5O/1GJH, exhibit similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, suggest differences in antiapoptotic activity for the two isoforms
Role in disease
The Bcl-2 gene has been implicated in a number of cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s, including melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
, breast
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, prostate
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, and lung carcinomas
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
, as well as schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
. It is also thought to be involved in resistance to conventional cancer treatment. This suggests that decreased apoptosis may play a role in the development of cancer.
Cancer occurs when the homeostatic balance between cell growth and death is disturbed. Research in cancer biology has discovered that a variety of aberrations in gene expression of anti-apoptotic, pro-apoptotic and BH3-only proteins can contribute to the many forms of the disease. An example can be seen in lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s. The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone does not cause cancer. But simultaneous over-expression of Bcl-2 and the proto-oncogene myc
Myc
Myc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases...
may produce aggressive B-cell malignancies including lymphoma.
In follicular lymphoma
Follicular lymphoma
Follicular lymphoma is the most common of the indolent non-Hodgkin's lymphomas, and the second most common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells , which has at least a partially follicular pattern...
, a chromosomal translocation
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
commonly occurs between the fourteenth and the eighteenth chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s—t(14;18)—which places the Bcl-2 gene next to the immunoglobulin heavy chain locus. This fusion gene is deregulated, leading to the transcription of excessively high levels of Bcl-2. This decreases the propensity of these cells for undergoing apoptosis.
Apoptosis also plays a very active role in regulating the immune system. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the case of defective apoptosis, it may contribute to etiological aspects of autoimmune diseases. The autoimmune disease, type 1 diabetes can be caused by defective apoptosis, which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s are the most important antigen presenting cells of the immune system, their activity must be tightly regulated by such mechanisms as apoptosis. Researchers have found that mice containing dendritic cells that are Bim
BCL2L11
Bcl-2-like protein 11 is a protein that in humans is encoded by the BCL2L11 gene.-Interactions:BCL2L11 has been shown to interact with DYNLL1, MCL1, BCL2-like 1, BCL2L2 and Bcl-2.-Further reading:...
-/-, thus unable to induce effective apoptosis, obtain autoimmune diseases more so than those that have normal dendritic cells. Other studies have shown that the lifespan of dendritic cells may be partly controlled by a timer dependent on anti-apoptotic Bcl-2.
Apoptosis plays a very important role in regulating a variety of diseases that have enormous social impacts. For example, schizophrenia is a neurodegenerative disease that may result from an abnormal ratio of pro- and anti-apoptotic factors. There is some evidence that this defective apoptosis may result from abnormal expression of Bcl-2 and increased expression of caspase-3.
Further research into the family of Bcl-2 proteins will provide a more complete picture on how these proteins interact with each other to promote and inhibit apoptosis. An understanding of the mechanisms involved may help develop new therapies for treating cancer, autoimmune conditions, and neurological diseases.
Diagnostic use
Antibodies to Bcl-2 can be used with immunohistochemistryImmunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
to identify cells containing the antigen. In healthy tissue, these antibodies will react with B-cells in the mantle zone
Mantle zone
The mantle zone of a lymphatic nodule is an outer ring of small lymphocytes surrounding a germinal center.It is also known as the "corona".It contains transient lymphocytes....
, as well as some T-cells. However, there is a considerable increase in positive cells in follicular lymphoma
Follicular lymphoma
Follicular lymphoma is the most common of the indolent non-Hodgkin's lymphomas, and the second most common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells , which has at least a partially follicular pattern...
, as well as many other forms of cancer. In some cases, the presence or absence of Bcl-2 staining in biopsies
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
may be significant for the patient's prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
or likelihood of relapse
Relapse
Relapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
.
Genasense
An antisense oligonucleotideOligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
drug Genasense (G3139) has been developed by Genta Incorporated
Genta (company)
Genta Inc. is a biopharmaceutical company based in Berkeley Heights, New Jersey, United States, which develops products for the treatment of patients with cancer.Its products include:*Genasense...
to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed.
It was shown that the proliferation of human lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
(with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.
These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004
By the first quarter 2010, Genasense had not received FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approval due to disappointing results in a melanoma trial. Although safety and efficacy of Genasense have not been established for any use, Genta Incorporated still claims on its website that studies are currently underway to examine the potential role of Genasense in a variety of clinical indications.
ABT-737
Abbott LaboratoriesAbbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
described in the mid-2000s a novel inhibitor of Bcl-2, Bcl-xL and Bcl-w, known as ABT-737. ABT-737 is one among many so-called BH3 mimetic small molecule inhibitors (SMI) targeting Bcl-2 and Bcl-2-related proteins such as Bcl-xL and Bcl-w but not A1 and Mcl-1, which may prove valuable in the therapy of lymphoma and other blood cancers.
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 RAD9A
RAD9A
Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by the RAD9A gene.-Interactions:RAD9A has been shown to interact with RAD17, HDAC1, TOPBP1, RAD1 homolog, BCL2-like 1, Bcl-2, Androgen receptor, DNAJC7, HUS1 and Abl gene.-Further reading:...
, BAK1, Reticulon 4
Reticulon 4
Reticulon-4, also known as Neurite outgrowth inhibitor or Nogo, is a protein that in humans is encoded by the RTN4 gene that has been identified as an inhibitor of neurite outgrowth specific to the central nervous system....
, Bcl-2-associated X protein
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....
, Caspase 8
Caspase 8
Caspase 8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase 3.CASP8 orthologs have been identified in numerous mammals for which complete genome data are available...
, BECN1
BECN1
Beclin-1 is a protein that in humans is encoded by the BECN1 gene.Beclin-1 is also known as autophagy-related gene 6. Beclin-1 and its binding partner class III phosphoinositide 3-kinase , also named Vps34, are required for the initiation of the formation of the autophagasome in...
, SOD1
SOD1
Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or SOD1 is an enzyme that in humans is encoded by the SOD1 gene. SOD1 is one of three human superoxide dismutases.- Function :...
, Bcl-2-interacting killer
Bcl-2-interacting killer
Bcl-2-interacting killer is a protein that in humans is encoded by the BIK gene.-Interactions:Bcl-2-interacting killer has been shown to interact with BCL2-like 1 and Bcl-2.-Further reading:...
, BH3 interacting domain death agonist
BH3 interacting domain death agonist
The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology domains , and can form hetero- or homodimers...
, RRAS
RRAS
Ras-related protein R-Ras is a protein that in humans is encoded by the RRAS gene.-Interactions:RRAS has been shown to interact with RASSF5, NCK1, Bcl-2, ARAF and RALGDS.-Further reading:...
, C-Raf
C-Raf
RAF proto-oncogene serine/threonine-protein kinase also known as proto-oncogene c-RAF or simply c-Raf is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade...
, BCL2L11
BCL2L11
Bcl-2-like protein 11 is a protein that in humans is encoded by the BCL2L11 gene.-Interactions:BCL2L11 has been shown to interact with DYNLL1, MCL1, BCL2-like 1, BCL2L2 and Bcl-2.-Further reading:...
, BNIPL
BNIPL
Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein is a protein that in humans is encoded by the BNIPL gene.-Interactions:BNIPL has been shown to interact with Macrophage migration inhibitory factor, GFER, CDC42, BCL2-like 1 and Bcl-2....
, HRK
HRK (gene)
Activator of apoptosis harakiri is a protein that in humans is encoded by the HRK gene.-Interactions:HRK has been shown to interact with BCL2-like 1 and Bcl-2.-Further reading:...
, PSEN1
PSEN1
Presenilin-1 is a protein that in humans is encoded by the PSEN1 gene.- Function :Alzheimer's disease patients with an inherited form of the disease carry mutations in the presenilin proteins or the amyloid precursor protein...
, BMF
BMF (gene)
Bcl-2-modifying factor is a protein that in humans is encoded by the BMF gene.-Interactions:BMF has been shown to interact with Bcl-2 and DYNLL2.-Further reading:...
, BNIP2
BNIP2
BCL2/adenovirus E1B 19 kDa protein-interacting protein 2 is a protein that in humans is encoded by the BNIP2 gene.-Interactions:BNIP2 has been shown to interact with CDC42, ARHGAP1 and Bcl-2.-Further reading:...
, BNIP3
BNIP3
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein that in humans is encoded by the BNIP3 gene.-Interactions:BNIP3 has been shown to interact with CD47, BCL2-like 1 and Bcl-2.-Further reading:...
, Nerve Growth factor IB
Nerve Growth factor IB
The nerve Growth factor IB also known as Nur77 or NR4A1 is a protein that in humans is encoded by the NR4A1 gene....
, 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,...
, Myc
Myc
Myc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases...
, BCAP31
BCAP31
B-cell receptor-associated protein 31 is a protein that in humans is encoded by the BCAP31 gene.-Interactions:BCAP31 has been shown to interact with Caspase 8, VAMP3, BCL2-like 1, Bcl-2 and Amyloid precursor protein.-Further reading:...
, SMN1
SMN1
Survival motor neuron protein is a protein that in humans is encoded by the SMN1 gene.-Interactions:SMN1 has been shown to interact with Gem-associated protein 7, GEMIN4, KPNB1, Survival of motor neuron protein-interacting protein 1, DDX20, Coilin, Small nuclear ribonucleoprotein D1, Fibrillarin,...
, CAPN2
CAPN2
Calpain-2 catalytic subunit is a protein that in humans is encoded by the CAPN2 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...
, PPP2CA
PPP2CA
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is an enzyme that in humans is encoded by the PPP2CA gene.-Interactions:...
, Noxa
Noxa
Phorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the PMAIP1 gene.Noxa is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members can form hetero- or homodimers, and they act as anti- or pro-apoptotic regulators that are involved in a wide...
, Cdk1
Cdk1
Cyclin dependent kinase 1 also known as Cdk1 or cell division control protein 2 homolog is a highly conserved protein that functions as a serine/threonine kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S....
, TP53BP2
TP53BP2
Apoptosis-stimulating of p53 protein 2 also known as Bcl2-binding protein and tumor suppressor p53-binding protein 2 is a protein that in humans is encoded by the TP53BP2 gene...
, Bcl-2-associated death promoter
Bcl-2-associated death promoter
The Bcl-2-associated death promoter 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...
and IRS1
IRS1
Insulin receptor substrate 1 is a protein that in humans is encoded by the IRS-1 gene.-Function:Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 receptors to intracellular pathways PI3K / Akt and Erk MAP kinase...
.
Human BCL-2 genes
BAKBcl-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....
; BAK1; 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....
; BCL2; BCL2A1
BCL2A1
Bcl-2-related protein A1 is a protein that in humans is encoded by the BCL2A1 gene.-Interactions:BCL2-related protein A1 has been shown to interact with Bcl-2-associated death promoter and Bcl-2-associated X protein.-Further reading:...
; BCL2L1; BCL2L10
BCL2L10
Bcl-2-like protein 10 is a protein that in humans is encoded by the BCL2L10 gene.-Further reading:...
; BCL2L13
BCL2L13
BCL2-like 13 , also known as BCL2L13 or Bcl-rambo, is a protein which in humans is encoded by the BCL2L13 gene.- Function :Bcl-rambo is a member of the Bcl-2 family of proteins that regulate apoptosis...
;
BCL2L14
BCL2L14
Apoptosis facilitator Bcl-2-like protein 14 is a protein that in humans is encoded by the BCL2L14 gene.-Further reading:...
; 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...
; BCL2L7P1; BOK
BOK (gene)
Bcl-2-related ovarian killer protein is a protein that in humans is encoded by the BOK gene.-Further reading:...
; 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...
; LGALS7 (Galectin-7)
See also
- ApoptosisApoptosisApoptosis 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...
- ApoptosomeApoptosomeThe apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal or external cell death stimulus...
- Bcl-2 homologous antagonist killerBcl-2 homologous antagonist killerBcl-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....
(BAK) - Bcl-2-associated X proteinBcl-2-associated X proteinThe 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....
(BAX) - BH3 interacting domain death agonistBH3 interacting domain death agonistThe BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology domains , and can form hetero- or homodimers...
(BID) - Caspases
- Cytochrome cCytochrome cThe 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...
- NoxaNoxaPhorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the PMAIP1 gene.Noxa is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members can form hetero- or homodimers, and they act as anti- or pro-apoptotic regulators that are involved in a wide...
- MitochondrionMitochondrionIn cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
- Microphthalmia-associated transcription factorMicrophthalmia-associated transcription factorMicrophthalmia-associated transcription factor is a basic helix-loop-helix leucine zipper transcription factor involved in melanocyte and osteoclast development.-Clinical significance:...
- p53 upregulated modulator of apoptosisP53 upregulated modulator of apoptosisThe p53 upregulated modulator of apoptosis also known as Bcl-2-binding component 3 , is a pro-apoptotic protein, member of the Bcl-2 protein family. In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene....
(PUMA)