Abstract:
:The Rho family small GTPases of the Ras superfamily play key roles in regulating diverse signaling pathways that control a myriad of fundamental cellular processes such as cytoskeletal dynamics, cell cycle progression, gene expression, cell polarity, migration and cell transformation. The Rho GTPases cycle between an active GTP-bound and an inactive GDP-bound form, which is controlled by many regulators including GEFs, GAPs and GDIs. Recent studies have revealed a new layer of regulation for Rho GTPases, indicating that several members of the Rho family of small GTPases including RhoA, Rac1, and RhoBTB, as well as the Ras family member Rap1B, are also regulated by the ubiquitin-proteasome pathway, which plays important roles in controlling cell polarity, migration, cell transformation and actin dynamics. Importantly, regulators for Rho GTP-GDP cycling such as RhoGDI and Rho-GEF ECT2 were also found to be modulated by the ubiquitin pathway. In this review, we focus on how ubiquitin signaling guides the fate and function of Rho GTPases and their regulators, especially how the E3 ubiquitin ligase Smurf1 regulates cell polarity and motility through targeting RhoA for ubiquitination and degradation.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Ding F,Yin Z,Wang HRdoi
10.2174/156802611798281357subject
Has Abstractpub_date
2011-12-01 00:00:00pages
2879-87issue
23eissn
1568-0266issn
1873-4294pii
BSP/CTMC/E-Pub/-000196-11-23journal_volume
11pub_type
杂志文章,评审abstract::There exists a huge attrition rate of molecules in clinical trials. It was expected that high-throughput screening and combinatorial chemistry would make the task of producing drugs easier. However, the efforts of the past decade have not been an unvarnished success. As a result, a lot of experimental and computationa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023392968
更新日期:2002-12-01 00:00:00
abstract::A large number of human disorders are caused by defects in protein folding resulting from genetic mutations or adverse physiological conditions, and these are collectively referred to protein misfolding diseases. Such disorders imply dysfunction of a cellular process either as a result of a toxic gain of function due ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611212220002
更新日期:2012-01-01 00:00:00
abstract::Combinatorial chemistry has had a major impact on the discovery and optimisation of potential lead compounds. This review details some of the fundamental principles behind combinatorial chemistry and describes a variety of methods employed in the search for new therapeutically interesting compounds including the conce...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451113
更新日期:2004-01-01 00:00:00
abstract::The atomic determination of the acetylcholine binding protein (AChBP), a molluscan cholinergic protein, homologous to the amino-terminal extracellular domain of nicotinic receptors (nAChRs), offers opportunities for the modeling of the acetylcholine binding site and its ligands. Recently, we constructed three-dimensio...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451177
更新日期:2004-01-01 00:00:00
abstract::Following the cloning of the classical opioid receptors (mu, delta and kappa), the opioid receptor like-1 (ORL-1) was identified as a G-protein coupled receptor (GPCR) with 65% structure homology to the other members of the opioid family. Its endogenous ligand nociception/orphanin FQ (N/OFQ) was discovered shortly the...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608786264227
更新日期:2008-01-01 00:00:00
abstract::Thematic Analysis™ is a chemogenomic tool which has been developed and used to aid the process of GPCR drug discovery. This review covers the scientific rationale behind the development of this tool and provides examples of the successful application of the chemogenomic method in both hit finding and hit to lead stage...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611796391302
更新日期:2011-01-01 00:00:00
abstract:: ...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
doi:10.2174/156802661921191024120954
更新日期:2019-01-01 00:00:00
abstract::The neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) family of hormones exhibit a wide variety of biological actions on the mammalian gastrointestinal tract through known G-protein coupled receptor pathways. At least four receptor subtypes, denoted as Y(1), Y(2), Y(4) an Y(5), each with specific ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607782340966
更新日期:2007-01-01 00:00:00
abstract::The H(3) histamine receptor is expressed in many brain regions, including those involved in sleep/wake regulation and cognitive functions. Inhibition of the H(3) receptor leads to increased release of multiple neurotransmitters in these regions, making this receptor an ideal target for the potential enhancement of aro...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610790411027
更新日期:2010-01-01 00:00:00
abstract::Hepatitis C virus (HCV) is a major cause of acute hepatitis and chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). No vaccine is currently available to prevent hepatitis C, and the current standard of care (SOC) - pegylated interferon-α (PEG-IFN-α) in combination with ribavirin (RBV) - is o...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610792232051
更新日期:2010-01-01 00:00:00
abstract::The Human Genome Project and the explosion of high-throughput data have transformed the areas of molecular and personalized medicine, which are producing a wide range of studies and experimental results and providing new insights for developing medical applications. Research in many interdisciplinary fields is resulti...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611313050002
更新日期:2013-01-01 00:00:00
abstract::In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance prob...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666140808125728
更新日期:2014-01-01 00:00:00
abstract::The connection of microbial biosynthetic gene clusters to the small molecule metabolites they encode is central to the discovery and characterization of new metabolic pathways with ecological and pharmacological potential. With increasing microbial genome sequence information being deposited into publicly available da...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666151012111046
更新日期:2016-01-01 00:00:00
abstract::Prenatal alcohol (ethanol) exposure (PAE) is the underlying cause for a variety of birth defects and neurodevelopmental deficits referred to as "Fetal Alcohol Spectrum Disorders (FASD)". The more visible phenotypes caused by PAE include growth retardation, and characteristic craniofacial abnormalities associated with ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160414124816
更新日期:2017-01-01 00:00:00
abstract::Ascidians (tunicates; sea squirts) are marine animals which provide a source of diverse, bioactive natural products, and a model for toxicity screenings. Compounds isolated from ascidians comprise an approved anti-tumor drug and many others are potent drug leads. Furthermore, the use of invertebrate embryos for toxico...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170130104922
更新日期:2017-01-01 00:00:00
abstract::In this paper we applied the "macromolecular docking" procedure to perform molecular modeling with the aim of screening transcription factor sequences for possible interaction to the HIV-1 TAR-RNA, employing the software Hex version 4.2. The molecular modeling data were compared with electrophoretic mobility shift ass...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612800166800
更新日期:2012-01-01 00:00:00
abstract::Variable selection is a procedure used to select the most important features to obtain as much information as possible from a reduced amount of features. The selection stage is crucial. The subsequent design of a quantitative structure-activity relationship (QSAR) model (regression or discriminant) would lead to poor ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608786786552
更新日期:2008-01-01 00:00:00
abstract::The adenosine A(2A) receptor is a member of the G protein-coupled receptor family and mediates multiple physiological effects of adenosine, both at the central nervous system and at peripheral tissues. Increasing evidence relates the A(2A) receptor with several pathological conditions such as neurodegenerative disorde...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610791268765
更新日期:2010-01-01 00:00:00
abstract::The emergence of multi-resistant bacteria to drugs is recognized as a major cause of the increasing number of deaths in hospitals. Killing these bacteria require multiple expensive drugs that can have side effects. Metal nanoparticles may provide a new strategy to combat them. Due the antimicrobial and antiviral prope...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150414141601
更新日期:2015-01-01 00:00:00
abstract::Inflammation is a complex phenomenon necessary in human defense mechanisms but also involved in the development of some human diseases. The discovery of cyclooxygenase-2 (COX- 2) improved the pharmacology of nonsteroidal anti-inflammatory drugs (NSAID) giving a clear mechanism for prostaglandin regulation in vivo and ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170821124947
更新日期:2017-01-01 00:00:00
abstract::Pyrimidine and purine nucleosides and their derivatives have critical functions and pharmacological applications in the brain. Nucleosides and nucleobases are precursors of nucleotides, which serve as the energy-rich currency of intermediary metabolism and as precursors of nucleic acids. Nucleosides (e.g., adenosine) ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611795347582
更新日期:2011-01-01 00:00:00
abstract::Bacterial infections constitute an always growing health problem worldwide. The resistance to antibiotics of an increasing number of bacterial pathogens necessitates a permanent search for new molecules with different mechanisms of action. Histidine biosynthesis is an ancient pathway found in bacteria, archaebacteria,...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160413140000
更新日期:2016-01-01 00:00:00
abstract::Alpha-particles are of considerable growing interest for Targeted Alpha Therapy (TAT). TAT gains more attention as new targets, chemical labeling techniques and α-particle emitters are developed but translation of TAT into the clinic has been slow, in part because of the limited availability and the short physical hal...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611212230002
更新日期:2012-01-01 00:00:00
abstract::As master regulators of lipid metabolism the peroxisome proliferator activated receptor (PPAR) family controls a wide variety of cellular processes, and thus it is not surprising that a large effort has focussed on discovering agents to pharmacologically modulate activity of these receptors. Early generation PPAR liga...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026033451673
更新日期:2003-01-01 00:00:00
abstract::Characteristic symptoms of schizophrenia and bipolar disorders have been described and classified about a century ago. Each of these disorders may cause considerable impairment reflecting substantial alterations in cognition, perception, and mood. Though both disease concepts are well established, psychopharmacologica...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113136660165
更新日期:2013-01-01 00:00:00
abstract::For effective tumour imaging by magnetic resonance imaging (MRI) there is a clear need to develop organ, tissue and cell specific contrast agents that can selectively bind to tumour biomarkers. The versatility of a range of bioconjugation techniques and facile coupling chemistries has facilitated the synthesis of MRI ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610791384199
更新日期:2010-01-01 00:00:00
abstract::RNA interference (RNAi) is an attractive phenomenon for practical use that specifically inhibits gene expression and is carried out by small double-stranded RNAs (dsRNAs) including small interfering RNA (siRNA) or short hairpin RNA (shRNA). In addition, RNAi is of great interest for clinical use to cure refractory dis...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802609789630857
更新日期:2009-01-01 00:00:00
abstract::Despite the tremendous progress in the field of drug designing, discovering a new drug molecule is still a challenging task. Drug discovery and development is a costly, time consuming and complex process that requires millions of dollar and 10-15 years to bring new drug molecules in the market. This huge investment an...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611313100005
更新日期:2013-01-01 00:00:00
abstract::At present, a limited number of strategies exist for diagnostic imaging of patients with bacterial infection. While radiolabeled probes and white blood cells provide robust solutions to detect bacteria in humans, they also give false positives in cases of sterile inflammation. With the onset of bacterial drug resistan...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611313040008
更新日期:2013-01-01 00:00:00
abstract::Research over the years has gradually and sequentially highlighted contributory role of hypothalamic- based kisspeptin-signaling axis as a major positive modulator of the neuroendocrinological reproductive axis in mammals. However, a series of landmark studies provided convincing evidence of role of this signaling in ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160212123309
更新日期:2016-01-01 00:00:00