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In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.
CREB-TF is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.
A leucine zipper is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amino acid segment and the display of these amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The polypeptide segments containing these periodic arrays of leucine residues were proposed to exist in an alpha-helical conformation and the leucine side chains from one alpha helix interdigitate with those from the alpha helix of a second polypeptide, facilitating dimerization.
Cyclic adenosine monophosphate Response Element Binding protein Binding Protein, also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the CREBBP gene in humans, located on chromosome 16p13.3. CBP has intrinsic acetyltransferase functions; it is able to add acetyl groups to both transcription factors as well as histone lysines, the latter of which has been shown to alter chromatin structure making genes more accessible for transcription. This relatively unique acetyltransferase activity is also seen in another transcription enzyme, EP300 (p300). Together, they are known as the p300-CBP coactivator family and are known to associate with more than 16,000 genes in humans; however, while these proteins share many structural features, emerging evidence suggests that these two co-activators may promote transcription of genes with different biological functions.
Activating transcription factor, ATF, is a group of bZIP transcription factors, which act as homodimers or heterodimers with a range of other bZIP factors. First, they have been described as members of the CREB/ATF family, whereas it turned out later that some of them might be more similar to AP-1-like factors such as c-Jun or c-Fos. In general, ATFs are known to respond to extracellular signals and this suggests an important role that they have in maintaining homeostasis. Some of these ATFs, such as ATF3, ATF4, and ATF6 are known to play a role in stress responses. Another example of ATF function would be ATFx that can suppress apoptosis.
CAMP responsive element binding protein 1, also known as CREB-1, is a protein that in humans is encoded by the CREB1 gene. This protein binds the cAMP response element, a DNA nucleotide sequence present in many viral and cellular promoters. The binding of CREB1 stimulates transcription.
Cyclic AMP-dependent transcription factor ATF-3 is a protein that, in humans, is encoded by the ATF3 gene.
Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.
Activating transcription factor 4 , also known as ATF4, is a protein that in humans is encoded by the ATF4 gene.
Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.
Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.
cAMP responsive element modulator is a protein that in humans is encoded by the CREM gene, and it belongs to the cAMP-responsive element binding protein family. It has multiple isoforms, which act either as repressors or activators. CREB family is important for in regulating transcription in response to various stresses, metabolic and developmental signals. CREM transcription factors also play an important role in many physiological systems, such as cardiac function, circadian rhythms, locomotion and spermatogenesis.
Cyclic AMP-responsive element-binding protein 3 is a protein that in humans is encoded by the CREB3 gene.
Activating transcription factor 5, also known as ATF5, is a protein that, in humans, is encoded by the ATF5 gene.
CAMP responsive element binding protein-like 1, also known as CREBL1, is a protein which in humans is encoded by the CREBL1 gene.
Cyclic AMP-dependent transcription factor ATF-7 is a protein that in humans is encoded by the ATF7 gene.
Cyclic AMP-responsive element-binding protein 5 is a protein that in humans is encoded by the CREB5 gene.
The cellular transcription factor CREB helps learning and the stabilization and retrieval of fear-based, long-term memories. This is done mainly through its expression in the hippocampus and the amygdala. Studies supporting the role of CREB in cognition include those that knock out the gene, reduce its expression, or overexpress it.
The Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors.
Alcoholism is a chronic disease characterized by trouble controlling the consumption of alcohol, dependence, and withdrawal upon rapid cessation of drinking. According to ARDI reports approximately 88,000 people had alcohol-related deaths in the United States between the years of 2006 and 2010. Furthermore, chronic alcohol use is consistently the third leading cause of death in the United States. In consequence, research has sought to determine the factors responsible for the development and persistence of alcoholism. From this research, several molecular and epigenetic mechanisms have been discovered.
References
- ↑ Targeted mutation of the CREB gene: Compensation within the CREB/ATF family of transcription factors EDITH HUMMLER, TIMOTHY J. COLE, JULIE A. BLENDY, RUTH GANSS, ADRIANO AGUZZII, WOLFGANG SCHMID, FRIEDRICH BEERMANN, AND GÜNTHER SCHÜTZ Proc. Nati. Acad. Sci. USA. Vol. 91, pp. 5647-5651, June 1994, Biochemistry
- ↑ Karin M1, Smeal T (1992). "Control of transcription factors by signal transduction pathways: the beginning of the end". Trends Biochem Sci. 17 (10): 418–22. doi:10.1016/0968-0004(92)90012-x. PMID 1455510.
- ↑ "Classification of Human Transcription Factors (TFClass)". Archived from the original on 2014-04-07.
- ↑ Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. pp. 125–126. ISBN 1-4160-2328-3.