BTG2
Encyclopedia
Protein BTG2 also known as BTG family member 2 or NGF-inducible anti-proliferative protein PC3 or NGF-inducible protein TIS21, is a protein
that in humans is encoded by the BTG2 gene
(B-cell translocation gene 2) and in other mammals by the homologous Btg2 gene. This protein controls cell cycle
progression and proneural genes expression by acting as a transcription coregulator
that enhances or inhibits the activity of transcription factor
s.
The protein BTG2 is the human homolog of the PC3 (pheochromocytoma cell 3) protein in rat and of the Tis21 (tetradecanoyl phorbol acetate-inducible sequence 21) protein in mouse. Tis21 had been originally isolated as a sequence induced by TPA
in mouse fibroblasts, whereas PC3 was originally isolated as sequence induced at the beginning of neuron differentiation; BTG2 was then isolated in human cells as sequence induced by p53
and DNA damage.
The protein encoded by the gene BTG2 (which is the official name assigned to the gene PC3/Tis21/BTG2) is a member of the BTG/Tob family (that comprises six proteins BTG1
, BTG2/PC3/Tis21, BTG3
/ANA, BTG4
/PC3B, Tob1
/Tob and Tob2
). This family has structurally related proteins that appear to have antiproliferative properties. In particular, the BTG2 protein has been shown to negatively control a cell cycle checkpoint at the G1
to S phase
transition in fibroblasts and neuronal cells by direct inhibition of the activity of cyclin D1
promoter.
generated during adulthood, in the two neurogenic regions of adult brain, i.e., the hippocampus and the subventricular zone. Such requirement of BTG2 in neuron maturation is consistent with the fact that during brain development BTG2 is expressed in the proliferating neuroblasts of the ventricular zone of the neural tube, and to a lower extent in the differentiating neuroblasts of the mantle zone; postnatally it is expressed in cerebellar precursors mainly in the proliferating regions of the neuropithelium (i.e., in the external granular layer), and in the hippocampus in proliferating and differentiating progenitor cells. The pro-differentiative action of BTG2 appears to be consequent not only to inhibition of cell cycle progression but also to a BTG2-dependent activation of proneural genes in neural progenitor cells. In fact, BTG2 activates proneural genes by associating with the promoter of Id3
, a key inhibitor of proneural gene activity, and by negatively regulating its activity.
BTG2 is a transcriptional cofactor, given that it has been shown to associate with, and regulate the promoters not only of Id3 but also of cyclin D1
and RAR-β
, being part of transcriptional complexes. Interestingly, it has been shown that when the differentiation of new neurons of the hippocampus - a brain region important for learning and memory - is either accelerated or delayed by means of overexpression or deletion of BTG2, respectively, spatial and contextual memory is heavily altered. This suggests that the time the young neurons spend in different states of neuronal differentiation is critical for their ultimate function in learning and memory, and that BTG2 may play a role in the timing of recruitment of the new neuron into memory circuits.
with PRMT1
, HOXB9
, CNOT8
and HDAC1
and HDAC4
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the BTG2 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...
(B-cell translocation gene 2) and in other mammals by the homologous Btg2 gene. This protein controls cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
progression and proneural genes expression by acting as a transcription coregulator
Transcription coregulator
In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that...
that enhances or inhibits the activity of transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s.
The protein BTG2 is the human homolog of the PC3 (pheochromocytoma cell 3) protein in rat and of the Tis21 (tetradecanoyl phorbol acetate-inducible sequence 21) protein in mouse. Tis21 had been originally isolated as a sequence induced by TPA
12-O-Tetradecanoylphorbol-13-acetate
12-O-tetradecanoylphorbol-13-acetate , also commonly known as tetradecanoylphorbol acetate, tetradecanoyl phorbol acetate, and phorbol 12-myristate 13-acetate , is diester of phorbol and a potent tumor promoter often employed in biomedical research to activate the signal transduction enzyme protein...
in mouse fibroblasts, whereas PC3 was originally isolated as sequence induced at the beginning of neuron differentiation; BTG2 was then isolated in human cells as sequence induced by p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
and DNA damage.
The protein encoded by the gene BTG2 (which is the official name assigned to the gene PC3/Tis21/BTG2) is a member of the BTG/Tob family (that comprises six proteins BTG1
BTG1
Protein BTG1 is a protein that in humans is encoded by the BTG1 gene.-Interactions:BTG1 has been shown to interact with CNOT7, HOXB9, PRMT1 and CNOT8.-Further reading:...
, BTG2/PC3/Tis21, BTG3
BTG3
Protein BTG3 is a protein that in humans is encoded by the BTG3 gene.-Further reading:...
/ANA, BTG4
BTG4
Protein BTG4 also known as BTG family member 4 is a protein that in humans is encoded by the BTG4 gene . BTG4 has anti-proliferative properties and can induce G1 cell cycle arrest....
/PC3B, Tob1
TOB1
Protein Tob1 is a protein that in humans is encoded by the TOB1 gene.-Interactions:TOB1 has been shown to interact with MARCKS, RPS6KA1, CNOT7, MAPK1 and Mitogen-activated protein kinase 9.-Further reading:...
/Tob and Tob2
TOB2
Protein Tob2 is a protein that in humans is encoded by the TOB2 gene.-Further reading:...
). This family has structurally related proteins that appear to have antiproliferative properties. In particular, the BTG2 protein has been shown to negatively control a cell cycle checkpoint at the G1
G1 phase
The G1 phase is a period in the cell cycle during interphase, before the S phase. For many cells, this phase is the major period of cell growth during its lifespan. During this stage new organelles are being synthesized, so the cell requires both structural proteins and enzymes, resulting in great...
to S phase
S phase
S-phase is the part of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Precise and accurate DNA replication is necessary to prevent genetic abnormalities which often lead to cell death or disease. Due to the importance, the regulatory pathways that govern this...
transition in fibroblasts and neuronal cells by direct inhibition of the activity of cyclin D1
Cyclin D1
G1/S-specific cyclin-D1 is a protein that in humans is encoded by the CCND1 gene.Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma.-Interactions:...
promoter.
BTG2, essential regulator of neuron differentiation
A number of studies in vivo have shown that BTG2 expression is associated with the neurogenic asymmetric division in neural progenitor cells. Moreover, when directly overexpressed in vivo in neural progenitor cells, BTG2 induces their differentiation. In fact, in the neuronal PC12 cell line BTG2 is not able to trigger differentiation by itself, but only to synergize with NGF, while in vivo BTG2 is fully able to induce differentiation of progenitor cells, i.e., during embryonic development in the neuroblast of the neural tube and in granule precursors of cerebellum, as well in adult progenitor cells of the dentate gyrus and of the subventricular zone. Notably, it has recently been shown that BTG2 is essential for the differentiation of new neurons, using a BTG2 knock out mouse. BTG2 is thus a pan-neural gene required for the development of the new neuronNeuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
generated during adulthood, in the two neurogenic regions of adult brain, i.e., the hippocampus and the subventricular zone. Such requirement of BTG2 in neuron maturation is consistent with the fact that during brain development BTG2 is expressed in the proliferating neuroblasts of the ventricular zone of the neural tube, and to a lower extent in the differentiating neuroblasts of the mantle zone; postnatally it is expressed in cerebellar precursors mainly in the proliferating regions of the neuropithelium (i.e., in the external granular layer), and in the hippocampus in proliferating and differentiating progenitor cells. The pro-differentiative action of BTG2 appears to be consequent not only to inhibition of cell cycle progression but also to a BTG2-dependent activation of proneural genes in neural progenitor cells. In fact, BTG2 activates proneural genes by associating with the promoter of Id3
ID3 (gene)
DNA-binding protein inhibitor ID-3 is a protein that in humans is encoded by the ID3 gene.-Interactions:ID3 has been shown to interact with TCF3.-Repressors of ID3:...
, a key inhibitor of proneural gene activity, and by negatively regulating its activity.
BTG2 is a transcriptional cofactor, given that it has been shown to associate with, and regulate the promoters not only of Id3 but also of cyclin D1
Cyclin D1
G1/S-specific cyclin-D1 is a protein that in humans is encoded by the CCND1 gene.Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma.-Interactions:...
and RAR-β
Retinoic acid receptor beta
Retinoic acid receptor beta , also known as NR1B2 is a nuclear receptor that in humans is encoded by the RARB gene.- Function :...
, being part of transcriptional complexes. Interestingly, it has been shown that when the differentiation of new neurons of the hippocampus - a brain region important for learning and memory - is either accelerated or delayed by means of overexpression or deletion of BTG2, respectively, spatial and contextual memory is heavily altered. This suggests that the time the young neurons spend in different states of neuronal differentiation is critical for their ultimate function in learning and memory, and that BTG2 may play a role in the timing of recruitment of the new neuron into memory circuits.
Interactions
BTG2 has been shown to interactProtein-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 PRMT1
PRMT1
Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene.-Interactions:PRMT1 has been shown to interact with BTG2, KHDRBS1, ILF3, HNRPK, BTG1, HNRNPR, IFNAR1, FUS, DHX9 and SUPT5H.-Further reading:...
, HOXB9
HOXB9
Homeobox protein Hox-B9 is a protein that in humans is encoded by the HOXB9 gene.-Interactions:HOXB9 has been shown to interact with BTG2 and BTG1....
, CNOT8
CNOT8
CCR4-NOT transcription complex subunit 8 is a protein that in humans is encoded by the CNOT8 gene.-Interactions:CNOT8 has been shown to interact with BTG2, BTG1, CNOT1 and CNOT3.-Further reading:...
and HDAC1
HDAC1
Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
and HDAC4
HDAC4
Histone deacetylase 4, also known as HDAC4, is a protein which in humans is encoded by the HDAC4 gene.- Function :Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects...
.