Abstract:
:Transcription factors comprise just over 7% of the human proteome and serve as gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated cell signaling pathways converge on transcription factors, decorating these proteins with an array of post-translational modifications (PTMs) that are often interdependent, being linked in time, space, and combinatorial function. These PTMs orchestrate every activity of a transcription factor over its entire lifespan--from subcellular localization to protein-protein interactions, sequence-specific DNA binding, transcriptional regulatory activity, and protein stability--and play key roles in the epigenetic regulation of gene expression. The multitude of PTMs of transcription factors also offers numerous potential points of intervention for development of therapeutic agents to treat a wide spectrum of diseases. We review PTMs most commonly targeting transcription factors, focusing on recent reports of sequential and linked PTMs of individual factors.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Filtz TM,Vogel WK,Leid Mdoi
10.1016/j.tips.2013.11.005subject
Has Abstractpub_date
2014-02-01 00:00:00pages
76-85issue
2eissn
0165-6147issn
1873-3735pii
S0165-6147(13)00225-3journal_volume
35pub_type
杂志文章,评审abstract::Recent advances in schizophrenia (SZ) research indicate that the telencephalic gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with this psychiatric disorder probably is mediated by the hypermethylation of the glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A ph...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2008.10.010
更新日期:2009-02-01 00:00:00
abstract::Protease-activated receptors (PARs) are a ubiquitously expressed class of G-protein-coupled receptors (GPCRs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. PAR1 is the archetypal family member and has been the object of large-scale drug development programs...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.05.001
更新日期:2017-08-01 00:00:00
abstract::The broad importance of receptor-activated phosphoinositide hydrolysis in the physiological action of hormones, neurotransmitters and growth factors has sparked interest in the study of transmembrane signalling events responsible for activation of phospholipase C. As with receptors involved in regulation of adenylyl c...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(89)90008-4
更新日期:1989-09-01 00:00:00
abstract::The rigorous estimation of a dissociation constant (Kb) for antagonists in functional assays has been sought by pharmacologists using a variety of techniques ever since the regression method of Arunlakshana and Schild in 1959. Here, Michael Lew and James Angus describe a simplified global regression method with improv...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)89066-5
更新日期:1995-10-01 00:00:00
abstract::Epoxyeicosatrienoic acids (EETs), derived from arachidonic acid by cytochrome P450 epoxygenases, are potent vasodilators that function as endothelium-derived hyperpolarizing factors in some vascular beds. EETs are rapidly metabolized by soluble epoxide hydrolase to form dihydroxyeicosatrienoic acids (DHETs). Recent re...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.11.002
更新日期:2007-01-01 00:00:00
abstract::The affinity of a drug candidate for a biological membrane (its lipophilicity) is closely related to the pharmacologically crucial events of absorption, biodistribution, metabolization and excretion. The evolution of knowledge of biological membranes during the past two decades contrasts with the rudimentary parameter...
journal_title:Trends in pharmacological sciences
pub_type: 历史文章,杂志文章
doi:10.1016/j.tips.2010.06.007
更新日期:2010-10-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) comprise a large and diverse class of signal-transducing receptors that undergo dynamic and isoform-specific membrane trafficking. GPCRs thus have an inherent potential to initiate or regulate signaling reactions from multiple membrane locations. This review discusses emerging insig...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.11.009
更新日期:2018-02-01 00:00:00
abstract::Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intramitochondrial calcium (Ca(2+)) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca(2+) home...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2010.08.007
更新日期:2010-12-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2009.02.003
更新日期:2009-05-01 00:00:00
abstract::Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by gly...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/s0165-6147(99)01428-5
更新日期:2000-02-01 00:00:00
abstract::Chronic inflammation is the basis of various chronic illnesses including cancer and vascular diseases. However, much has yet to be learned how inflammation becomes chronic. Prostaglandins (PGs) are well established as mediators of acute inflammation, and recent studies in experimental animals have provided evidence th...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2012.02.004
更新日期:2012-06-01 00:00:00
abstract::Benzodiazepines in clinical use have a range of pharmacological activities. Some, e.g. sedation, tolerance and addiction, are not welcome. Undesirable side-effects of drugs are often controlled by developing compounds that bind more selectively to one particular receptor subtype. An alternative approach, discussed her...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(90)90126-s
更新日期:1990-11-01 00:00:00
abstract::Dimerization is fairly common in the G-protein-coupled receptor (GPCR) superfamily. First attempts to rationalize this phenomenon gave rise to an idea that two receptors in a dimer could be necessary to bind a single molecule of G protein or arrestin. Although GPCRs, G proteins and arrestins were crystallized only in ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2008.02.004
更新日期:2008-05-01 00:00:00
abstract::Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easil...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.10.014
更新日期:2017-02-01 00:00:00
abstract::Biogenic amines and amino acids have been implicated in central cardiovascular homeostasis. Initially, drugs were injected into the brain and their effects on blood pressure were investigated. Other approaches allowed endogenous neurotransmitters released in the extracellular space of brain structures involved in card...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:
更新日期:1996-10-01 00:00:00
abstract::The breast cancer resistance protein [BCRP (also known as ABCG2)] belongs to the ATP binding cassette (ABC) family of transmembrane drug transporters. BCRP has a broad substrate specificity and actively extrudes a wide variety of drugs, carcinogens and dietary toxins from cells. Situated in the apical plasma membrane ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.11.007
更新日期:2006-01-01 00:00:00
abstract::The alpha-adrenoceptor was subdivided into three subtypes: alpha 2A-, alpha 2B- and alpha 2C-adrenoceptors almost ten years ago. Since then, the search has been on to discover and develop subtype-selective agonists and antagonists, but as yet no major breakthrough has been made. In the past year, several strains of ge...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01063-8
更新日期:1997-06-01 00:00:00
abstract::Intercellular transfer of proteins is a mode of communication between cells that is crucial for certain physiological processes. Chemotherapy is the treatment of choice for approximately 50% of all cancers. However, multidrug resistance mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the effective...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.06.001
更新日期:2005-08-01 00:00:00
abstract::Disorders of the central nervous system (CNS) have many etiologies compounded by limited options for treatment. The lack of successful treatments for these disorders stems from the difficulty of gaining effective access to the CNS through the blood-brain barrier, and the irreplaceable nature of neurons. Here, we revie...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2019.04.013
更新日期:2019-07-01 00:00:00
abstract::Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(93)90064-Q
更新日期:1993-11-01 00:00:00
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journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)89023-9
更新日期:1995-06-01 00:00:00
abstract::Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and ch...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.12.004
更新日期:2014-03-01 00:00:00
abstract::It is now established that most of the approximately 800 G-protein-coupled receptors (GPCRs) are regulated by phosphorylation in a process that results in the recruitment of arrestins, leading to receptor desensitization and the activation of arrestin-dependent processes. This generalized view of GPCR regulation, howe...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2008.05.006
更新日期:2008-08-01 00:00:00
abstract::The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tach...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2003.11.005
更新日期:2004-01-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a pulmonary inflammatory disease that is caused by cigarette smoke. The main characteristic of COPD is the continued inflammation caused by the sustained influx of macrophages and neutrophils into the lung. Recent studies have shed light on how these cells are attracted ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2006.09.003
更新日期:2006-11-01 00:00:00
abstract::Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but the...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.02.001
更新日期:2013-04-01 00:00:00
abstract::The 5-HT7 receptor was among a group of 5-HT receptors that were discovered using targeted cloning strategies 12 years ago. This receptor is a seven-transmembrane-domain G-protein-coupled receptor that is positively linked to adenylyl cyclase. The distributions of 5-HT7 receptor mRNA, immunolabeling and radioligand bi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.07.002
更新日期:2004-09-01 00:00:00
abstract::Complete nucleotide sequences are now available for different species of the animal kingdom: Caenorhabditis elegans - a nematode, Drosophila - an insect, and humans - a mammal. Such information makes it possible to compare the set of nuclear receptors found in these organisms, and to discuss the possible reasons for t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01859-9
更新日期:2001-12-01 00:00:00
abstract::There is increasing awareness of the compartmentalization of cAMP signalling--the means by which cAMP levels change in discrete domains of the cell with discrete local consequences. Current developments in understanding the organization of adenylyl cyclases in the plasma membrane are illuminating how the earliest part...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.06.002
更新日期:2006-08-01 00:00:00
abstract::As we have learnt from earlier articles in our series on the pharmacology of excitatory amino acids, neurons and glia express several subtypes of excitatory amino acid receptor, the activation of which increases intracellular free calcium ion concentration. In this sixth article, Mark Mayer and Richard Miller detail t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(90)90254-6
更新日期:1990-06-01 00:00:00