Abstract:
:The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that inactivate tumor suppressors, hyperactivate oncogenes, and upregulate protein kinases, all of which promote Pol I transcription and drive cell proliferation. The intimate balance between Pol I transcription and growth-factor signaling is perturbed in cancer cells, indicating that upregulation of rRNA synthesis is mandatory for all tumors. Though the emerging picture of transcriptional regulation reveals an unexpected level of complexity, we are beginning to understand the multiple links between rRNA biogenesis and cancer. In this review, we discuss experimental data and potential strategies to downregulate rRNA synthesis and induce an antiproliferative response in cancer cells.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Drygin D,Rice WG,Grummt Idoi
10.1146/annurev.pharmtox.010909.105844subject
Has Abstractpub_date
2010-01-01 00:00:00pages
131-56eissn
0362-1642issn
1545-4304journal_volume
50pub_type
杂志文章,评审abstract::Recent advances in cell signaling research suggest that multiple sets of signal transducing molecules are preorganized and sequestered in distinct compartments within the cell. These compartments are assembled and maintained by specific cellular machinery. The molecular ecology within a compartment creates an environm...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.45.120403.095807
更新日期:2005-01-01 00:00:00
abstract::Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered inter...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010814-124316
更新日期:2016-01-01 00:00:00
abstract::CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G protein-coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.46.120604.141254
更新日期:2006-01-01 00:00:00
abstract::The beta 3 subtype of adrenaline and noradrenaline receptors has now been extensively characterized at the structural and functional levels. Ligand binding and adenylyl cyclase activation studies helped define a beta-adrenergic profile that is quite distinct from that of the beta 1- and beta 2-adrenergic receptors, bu...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.37.1.421
更新日期:1997-01-01 00:00:00
abstract::DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However, they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topo...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.41.1.53
更新日期:2001-01-01 00:00:00
abstract::Bisphosphonates (BPs) are pyrophosphate analogs in which the oxygen bridge has been replaced by carbon and diverse carbon side chains have generated a large family of compounds. Several are potent inhibitors of bone destruction (resorption) and are in clinical use for the treatment and prevention of osteoporosis, Page...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.38.1.375
更新日期:1998-01-01 00:00:00
abstract::The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.46.120604.141238
更新日期:2006-01-01 00:00:00
abstract::Arsenic is a naturally occurring metalloid and one of the few metals that can be metabolized inside the human body. The pervasive presence of arsenic in nature and anthropogenic sources from agricultural and medical use have perpetuated human exposure to this toxic and carcinogenic element. Highly exposed individuals ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章
doi:10.1146/annurev-pharmtox-030220-013418
更新日期:2021-01-06 00:00:00
abstract::Organophosphorus insecticide self-poisoning is a major global health problem, killing over 100,000 people annually. It is a complex multi-organ condition, involving the inhibition of cholinesterases, and perhaps other enzymes, and the effects of large doses of ingested solvents. Variability between organophosphorus in...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010818-021842
更新日期:2019-01-06 00:00:00
abstract::Exposure of the developing conceptus to selected environmental agents can lead to deleterious and often times lethal birth defects. These malformations result in serious emotional and financial consequences to families and societies worldwide. As we continue to progress technologically, we face challenges from the int...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.42.083001.110955
更新日期:2002-01-01 00:00:00
abstract::Originally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, an...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010716-104926
更新日期:2017-01-06 00:00:00
abstract::Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme ...
journal_title:Annual review of pharmacology and toxicology
pub_type:
doi:10.1146/annurev-pharmtox-091616-023708
更新日期:2017-01-06 00:00:00
abstract::The cost of drugs is a major and rapidly rising component of health-care expenditures. We survey recent literature on the ethics and economics of skyrocketing pharmaceutical prices and find that advances in economic research have increased the sharpness and focus of the ethically based calls to increase access by modi...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010814-124649
更新日期:2015-01-01 00:00:00
abstract::Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.38.1.97
更新日期:1998-01-01 00:00:00
abstract::Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and hav...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010716-104846
更新日期:2017-01-06 00:00:00
abstract::The developing central nervous system (CNS) is more vulnerable to injury than the adult one. Although a great deal of research has been devoted to subtle effects of developmental exposure, such as neurobehavioral changes, this review instead focuses on a number of chemicals that have been shown, in several experimenta...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.44.101802.121424
更新日期:2004-01-01 00:00:00
abstract::The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to cha...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.34.040194.001133
更新日期:1994-01-01 00:00:00
abstract::Research on autophagy and its effects on cell metabolism and physiology has increased dramatically during recent years. Multiple forms of autophagy have been characterized, and many of the genes involved in the regulation of this process have been identified. The importance of autophagy for embryonic development and m...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-011112-140210
更新日期:2013-01-01 00:00:00
abstract::The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cue...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.47.120505.105208
更新日期:2007-01-01 00:00:00
abstract::Drug transporters are now widely acknowledged as important determinants governing drug absorption, excretion, and, in many cases, extent of drug entry into target organs. There is also a greater appreciation that altered drug transporter function, whether due to genetic polymorphisms, drug-drug interactions, or enviro...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010611-134529
更新日期:2012-01-01 00:00:00
abstract::Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.39.1.151
更新日期:1999-01-01 00:00:00
abstract::Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular saf...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010617-053110
更新日期:2018-01-06 00:00:00
abstract::This essay is an account of the author's experience in trying to interpret the action of drugs as seen in in vitro bioassays. The central theme is how the development of simple mathematical models has assisted in the interpretation of drug actions. Starting from encounters with partial agonists, the essay describes th...
journal_title:Annual review of pharmacology and toxicology
pub_type: 传,历史文章,杂志文章,评审
doi:10.1146/annurev.pa.36.040196.000245
更新日期:1996-01-01 00:00:00
abstract::Long-acting contraceptives are the most effective reversible contraceptive methods. Increasing patients' access to these contraceptives may translate into fewer unintended pregnancies and lead to substantial individual and public health benefits. However, development of long-acting products can be complex and challeng...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章
doi:10.1146/annurev-pharmtox-031120-015212
更新日期:2021-01-06 00:00:00
abstract::Ion channels and G protein-coupled receptors (GPCRs) are regulated by lipids in their membrane environment. Structural studies combined with biophysical and molecular simulation investigations reveal interaction sites for specific lipids on membrane protein structures. For K channels, PIP2 plays a key role in regulati...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010919-023411
更新日期:2020-01-06 00:00:00
abstract::Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010715-103801
更新日期:2016-01-01 00:00:00
abstract::Arterial tone is coordinated among vessel segments to optimize nutrient transport and organ function. Coordinated vasomotor activity is remarkable to observe and depends on stimuli, sparsely generated in tissue, eliciting electrical responses that conduct lengthwise among electrically coupled vascular cells. The condu...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev-pharmtox-010617-052623
更新日期:2018-01-06 00:00:00
abstract::Both pharmacologic and genetic methods are now available to manipulate intracellular levels of the protein thiol metallothionein. These approaches have begun to reveal the protective roles metallothioneins (MTs) have against oxygen, nitrogen, and carbon-centered free radicals, as well as the contributory role of MT to...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pa.35.040195.003223
更新日期:1995-01-01 00:00:00
abstract::The application of rapid methods currently used for screening discovery drug candidates for metabolism and pharmacokinetic characteristics is discussed. General considerations are given for screening in this context, including the criteria for good screens, the use of counterscreens, the proper sequencing of screens, ...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.40.1.133
更新日期:2000-01-01 00:00:00
abstract::Determining the potential toxicity of compounds early in the drug discovery process can be extremely beneficial in terms of both time and money conservation. Because of the speed of modern chemical synthesis and screening, to accurately evaluate the large number of compounds being produced, toxicology assays must have...
journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
doi:10.1146/annurev.pharmtox.40.1.335
更新日期:2000-01-01 00:00:00