Activating transcription factor 2
Encyclopedia
Activating transcription factor 2, also known as ATF2, is a protein
that, in humans, is encoded by the ATF2 gene
.
that is a member of the leucine zipper
family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun
and stimulates CRE-dependent transcription. The protein is also a histone acetyltransferase
(HAT) that specifically acetylates histones H2B and H4 in vitro; thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin
components. Additional transcript variants have been identified but their biological validity has not been determined.
The gene atf2 is located at human chromosome 2q32. The protein ATF-2 has 505 amino acids. Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton. ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38
and JNK. ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol
ester has been demonstrated.
Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors. ATF-2 may mediate oncogenesis caused by mutant Ras protein and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells.
ATF2 has also been shown to be phosphorylated at its N-terminal (Serine 472 and 480 in mouse; Serine 490 and 498 in human) by ATM upon double-stranded breaks. Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.
ATF2 has also been shown to be phosphorylated
at its N-terminal (serine 472 and 480 in mouse; serine 490 and 498 in human) by ATM
upon double-stranded breaks.
with
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 ATF2 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...
.
Function
This gene encodes a transcription factorTranscription 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...
that is a member of the leucine zipper
Leucine zipper
A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...
family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun
C-jun
c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
and stimulates CRE-dependent transcription. The protein is also a histone acetyltransferase
Histone acetyltransferase
Histone acetyltransferases are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine....
(HAT) that specifically acetylates histones H2B and H4 in vitro; thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
components. Additional transcript variants have been identified but their biological validity has not been determined.
The gene atf2 is located at human chromosome 2q32. The protein ATF-2 has 505 amino acids. Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton. ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38
P38 mitogen-activated protein kinases
P38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation and apoptosis....
and JNK. ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol
Phorbol
Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. It was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of Croton tiglium. Phorbol's structure was determined in 1967...
ester has been demonstrated.
Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors. ATF-2 may mediate oncogenesis caused by mutant Ras protein and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells.
ATF2 has also been shown to be phosphorylated at its N-terminal (Serine 472 and 480 in mouse; Serine 490 and 498 in human) by ATM upon double-stranded breaks. Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.
ATF2 has also been shown to be phosphorylated
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
at its N-terminal (serine 472 and 480 in mouse; serine 490 and 498 in human) by ATM
Ataxia telangiectasia mutated
Ataxia telangiectasia mutated is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis...
upon double-stranded breaks.
Interactions
Activating transcription factor 2 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
- C-junC-junc-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
, - Casein kinase 2, alpha 1,
- CREB binding proteinCREB binding proteinCREB-binding protein, also known as CREBBP or CBP, is a protein that in humans is encoded by the CREBBP gene.The CREB protein carries out its function by activating transcription, where interaction with transcription factors is managed by one or more of p300 domains: the nuclear receptor...
, - CSNK2A2CSNK2A2Casein kinase II subunit alpha is an enzyme that in humans is encoded by the CSNK2A2 gene.-Interactions:CSNK2A2 has been shown to interact with CSNK2B, FGF1, PTEN, RELA, ATF1, Nucleolin, CREB binding protein, Activating transcription factor 2, PIN1, C-jun and C-Fos.-Further reading:...
, - JDP2,
- MAPK14MAPK14Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.-Interactions:MAPK14 has been shown to interact with Casein kinase 2, alpha 1, RPS6KA4, MAPKAPK2, CDC25B, DUSP1, ZFP36L1, CDC25C, MAPKAPK3, Activating transcription factor 2, MAPK1,...
, - MAPK8MAPK8Mitogen-activated protein kinase 8 is an enzyme that in humans is encoded by the MAPK8 gene.-Interactions:MAPK8 has been shown to interact with SPIB, DUSP1, Activating transcription factor 2, SH3BP5, GSTP1, MAPK8IP1, MAP2K7, CRK, MAP2K4, DUSP22, Myc, MAP3K2, DUSP10, REL, MAPK8IP3, IRS1, MAP3K1 and...
, - Mothers against decapentaplegic homolog 3Mothers against decapentaplegic homolog 3Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins.The human SMAD3 gene is located on chromosome 15...
- NCOA6NCOA6Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.-Interactions:NCOA6 has been shown to interact with Ku70, RBBP5, E2F1, Retinoblastoma protein, CREB-binding protein, Activating transcription factor 2, HSF1, HBXIP, TGS1, TUBB, TUBA4A, Thyroid hormone receptor...
, - RUVBL2RUVBL2RuvB-like 2 , also known as RUVBL2, is a human gene coding for a protein belonging to the AAA+ family of proteins.-Interactions:RUVBL2 has been shown to interact with RuvB-like 1 and Activating transcription factor 2.-Further reading:...
, - UBE2IUBE2ISUMO-conjugating enzyme UBC9 is a protein that in humans is encoded by the UBE2I gene.-Interactions:UBE2I has been shown to interact with WT1, TOP1, RAD51, Activating transcription factor 2, PIAS1, SALL1, FHIT, RANBP2, Protein inhibitor of activated STAT2, DNMT3A, DNMT3B, Small ubiquitin-related...
.