Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Neurosci Bull ; 40(2): 218-240, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37253984

RESUMO

As the aging population continues to grow rapidly, age-related diseases are becoming an increasing burden on the healthcare system and a major concern for the well-being of elderly individuals. While aging is an inevitable process for all humans, it can be slowed down and age-related diseases can be treated or alleviated. Nicotinamide adenine dinucleotide (NAD) is a critical coenzyme or cofactor that plays a central role in metabolism and is involved in various cellular processes including the maintenance of metabolic homeostasis, post-translational protein modifications, DNA repair, and immune responses. As individuals age, their NAD levels decline, and this decrease has been suggested to be a contributing factor to the development of numerous age-related diseases, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. In pursuit of healthy aging, researchers have investigated approaches to boost or maintain NAD levels. Here, we provide an overview of NAD metabolism and the role of NAD in age-related diseases and summarize recent progress in the development of strategies that target NAD metabolism for the treatment of age-related diseases, particularly neurodegenerative diseases.


Assuntos
Doenças Cardiovasculares , Doenças Neurodegenerativas , Humanos , Idoso , NAD/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Envelhecimento/metabolismo , Homeostase
2.
Sci China Life Sci ; 65(12): 2354-2454, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36066811

RESUMO

Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on "healthy aging" raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels.


Assuntos
Doenças Cardiovasculares , Neoplasias , Humanos , Envelhecimento/genética , Envelhecimento/metabolismo , Neoplasias/genética
3.
Nat Commun ; 13(1): 4669, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945240

RESUMO

Medicinal applications of gold complexes have recently attracted attention due to their innovative antitumor mechanisms. In this work, two hypercoordinated carbon-centered gold clusters PAA4 and PAA5 are quantitatively synthesized by an intramolecular 6-exo-dig cyclization of polymetalated precursors. The on-bench and in vitro experimental studies demonstrate that the characteristic hypercarbon-tetragold(I) multi-center bonding in PAA4 and PAA5 not only guarantees their stability under common physiological conditions, but also facilitates a glutathione (GSH)-triggered prompt and synergetic release of active Au(I) ions in the GSH-overexpressed and acidic microenvironment of human bladder cancer EJ cells. The instantly massive release of coordination unsaturated Au(I) ions causes the efficient inhibition of thioredoxin reductases and then induces a rapid pro-oxidant response, consequently causing the occurrence of accelerated ferroptosis of EJ cells. As a result, these hypercarbon-centered gold(I) cluster prodrugs show high cytotoxicity to bladder cancer cell lines and thus exhibit a significant inhibition effect towards bladder tumors in vivo. Correlation of the synergetic domino dissociation of carbon-polymetal multi-center bonding in metal clusters with the accelerated ferroptosis of cancer cells provides a strategy for metallo-prodrugs and opens a broader prospect for the biological application of metal cluster compounds.


Assuntos
Ferroptose , Pró-Fármacos , Neoplasias da Bexiga Urinária , Carbono , Glutationa , Ouro/farmacologia , Humanos , Oxidantes , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio , Microambiente Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico
4.
Cell Res ; 32(6): 570-584, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35459935

RESUMO

The decline of nicotinamide adenine dinucleotide (NAD) occurs in a variety of human pathologies including neurodegeneration. NAD-boosting agents can provide neuroprotective benefits. Here, we report the discovery and development of a class of potent activators (NATs) of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway. We obtained the crystal structure of NAMPT in complex with the NAT, which defined the allosteric action of NAT near the enzyme active site. The optimization of NAT further revealed the critical role of K189 residue in boosting NAMPT activity. NATs effectively increased intracellular levels of NAD and induced subsequent metabolic and transcriptional reprogramming. Importantly, NATs exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity. These findings demonstrate the potential of NATs in the treatment of neurodegenerative diseases or conditions associated with NAD level decline.


Assuntos
NAD , Nicotinamida Fosforribosiltransferase , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Nicotinamida Fosforribosiltransferase/uso terapêutico
5.
Eur J Med Chem ; 236: 114260, 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35385807

RESUMO

NAMPT is the rate-limiting enzyme in the NAD salvage pathway, which makes it an attractive target for the treatment of many diseases associated with NAD exhaustion such as neurodegenerative diseases. Herein, we present the systematic optimization of NAT, an initial hit of NAMPT activator discovered by us through high-throughput screening, based on the co-crystal structure of the NAMPT-NAT complex. Over 80 NAT derivatives have been designed and synthesized, among which compound 72 showed notably improved potency as NAMPT activator and effectively protected cultured cells from FK866-mediated toxicity. Moreover, compound 72 exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity, which renders it a promising candidate for the development of novel neuroprotective agents.


Assuntos
NAD , Fármacos Neuroprotetores , Animais , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos , NAD/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Nicotinamida Fosforribosiltransferase/metabolismo
6.
Angew Chem Int Ed Engl ; 60(8): 4221-4230, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33155345

RESUMO

An unprecedented strain-driven dyotropic rearrangement of α-methylene-ß-lactones has been realized, which enables the efficient access of a wide range of α-methylene-γ-butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL-containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.

7.
J Vis Exp ; (143)2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30688306

RESUMO

Studying the function of a gene of interest can be achieved by manipulating its level of expression, such as decreasing its expression with knockdown cell lines or increasing its expression with overexpression cell lines. Transient and stable transfection are two methods that are often used for exogenous gene expression. Transient transfection is only useful for short-term expression, whereas stable transfection allows exogenous genes to be integrated into the host cell genome where it will be continuously expressed. As a result, stable transfection is usually employed for research into long-term genetic regulation. Here we describe a simple protocol to generate a stable cell line overexpressing tagged death receptor 3 (DR3) to explore DR3 function. We picked single clones after a retroviral infection in order to maintain the homogeneity and purity of the stable cell lines. The stable cell lines generated using this protocol render DR3-deficient HT29 cells sensitive to antimitotic drugs, thus reconstituting the apoptotic response in HT29 cells. Moreover, the FLAG tag on DR3 compensates for the unavailability of good DR3 antibody and facilitates the biochemical study of the molecular mechanism by which antimitotic agents induce apoptosis.


Assuntos
Antimitóticos/farmacologia , Apoptose , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HT29 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus
8.
Cell Res ; 28(5): 544-555, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29497138

RESUMO

The commonly used antimitotic chemotherapeutic agents such as taxol and vinblastine arrest cell cycle progression by disrupting mitotic spindles, and cause cancer cells to undergo apoptosis through 'mitotic catastrophe'. The molecular mechanisms by which these drugs induce apoptosis and their relevance to clinical efficacy are not known. Facilitated by a new spindle poison diazonamide, we found that apoptosis induced by these agents requires death receptor 3 (DR3). Mitotic arrest by these agents induces lysosome-dependent secretion of the DR3 ligand, TL1A. Engagement of TL1A with DR3 stimulates the formation of FADD-containing and caspase-8-containing death-inducing signaling complex (DISC), which subsequently activates apoptosis in cells that express DR3. Expression of DR3 and TL1A correlates with the apoptotic response of human tumor xenograft models and human cancer cell lines to antimitotic drugs, providing further evidence that these drugs kill cancer cells through the DR3/TL1A-mediated pathway. These results suggest that TL1A and DR3 may hold promise to be used as biomarkers for predicting clinical response to antimitotic therapeutics.


Assuntos
Antimitóticos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias/metabolismo , Neoplasias/patologia , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Comunicação Autócrina/efeitos dos fármacos , Caspase 8/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ligantes , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Camundongos Nus , Oxazóis/farmacologia , Paclitaxel/farmacologia , Proteínas Recombinantes/farmacologia
9.
Cell ; 158(6): 1324-1334, 2014 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-25215490

RESUMO

The P7C3 class of aminopropyl carbazole chemicals fosters the survival of neurons in a variety of rodent models of neurodegeneration or nerve cell injury. To uncover its mechanism of action, an active derivative of P7C3 was modified to contain both a benzophenone for photocrosslinking and an alkyne for CLICK chemistry. This derivative was found to bind nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme involved in the conversion of nicotinamide into nicotinamide adenine dinucleotide (NAD). Administration of active P7C3 chemicals to cells treated with doxorubicin, which induces NAD depletion, led to a rebound in intracellular levels of NAD and concomitant protection from doxorubicin-mediated toxicity. Active P7C3 variants likewise enhanced the activity of the purified NAMPT enzyme, providing further evidence that they act by increasing NAD levels through its NAMPT-mediated salvage.


Assuntos
NAD/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Carbazóis/farmacologia , Linhagem Celular Tumoral , Células Cultivadas , Citocinas/agonistas , Citocinas/genética , Citocinas/metabolismo , Doxorrubicina/farmacologia , Humanos , Redes e Vias Metabólicas , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo
10.
Nat Chem Biol ; 9(2): 84-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23292651

RESUMO

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) activates apoptosis through the death receptors DR4 and DR5. Because of its superior safety profile and high tumor specificity compared to other TNF family members, recombinant soluble TRAIL and agonistic antibodies against its receptors are actively being developed for clinical cancer therapy. Here, we describe the identification and characterization of the small molecules that directly target DR5 to initiate apoptosis in human cancer cells. The activity was initially discovered through a high-throughput chemical screen for compounds that promote cell death in synergy with a small-molecule mimetic of Smac, the antagonist for inhibitor of apoptosis protein. Structure-activity relationship studies yielded a more potent analog called bioymifi, which can act as a single agent to induce DR5 clustering and aggregation, leading to apoptosis. Thus, this study identified potential lead compounds for the development of small-molecule TRAIL mimics targeting DR5 for cancer therapy.


Assuntos
Neoplasias/tratamento farmacológico , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Apoptose , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Relação Dose-Resposta a Droga , Ativação Enzimática , Humanos , Cinética , Modelos Químicos , Ftalimidas/farmacologia , Ligação Proteica , RNA Interferente Pequeno/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Tiazolidinas/farmacologia
11.
Synlett ; 16(23): 2298-2310, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23226922

RESUMO

Isolated from the sponge Terpios hoshinota that causes coral black disease, nakiterpiosin was the first C-nor-D-homosteroid discovered from a marine source. We provide in this account an overview of the chemistry and biology of this natural product. We also include a short history of the synthesis of C-nor-D-homosteroids and the results of some unpublished biological studies of nakiterpiosin.

12.
Proc Natl Acad Sci U S A ; 109(42): 17010-5, 2012 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-23027934

RESUMO

We previously reported the discovery of P7C3, an aminopropyl carbazole having proneurogenic and neuroprotective properties in newborn neural precursor cells of the dentate gyrus. Here, we provide evidence that P7C3 also protects mature neurons in brain regions outside of the hippocampus. P7C3 blocks 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated cell death of dopaminergic neurons in the substantia nigra of adult mice, a model of Parkinson disease (PD). Dose-response studies show that the P7C3 analog P7C3A20 blocks cell death with even greater potency and efficacy, which parallels the relative potency and efficacy of these agents in blocking apoptosis of newborn neural precursor cells of the dentate gyrus. P7C3 and P7C3A20 display similar relative effects in blocking 1-methyl-4-phenylpyridinium (MPP(+))-mediated death of dopaminergic neurons in Caenorhabditis elegans, as well as in preserving C. elegans mobility following MPP(+) exposure. Dimebon, an antihistaminergic drug that is weakly proneurogenic and neuroprotective in the dentate gyrus, confers no protection in either the mouse or the worm models of PD. We further demonstrate that the hippocampal proneurogenic efficacy of eight additional analogs of P7C3 correlates with their protective efficacy in MPTP-mediated neurotoxicity. In vivo screening of P7C3 analogs for proneurogenic efficacy in the hippocampus may thus provide a reliable means of predicting neuroprotective efficacy. We propose that the chemical scaffold represented by P7C3 and P7C3A20 provides a basis for optimizing and advancing pharmacologic agents for the treatment of patients with PD.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/antagonistas & inibidores , 1-Metil-4-fenilpiridínio/antagonistas & inibidores , Carbazóis/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/prevenção & controle , Substância Negra/citologia , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans , Carbazóis/síntese química , Carbazóis/química , Carbazóis/farmacocinética , Relação Dose-Resposta a Droga , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Indóis/farmacocinética , Indóis/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Substância Negra/efeitos dos fármacos
13.
Proc Natl Acad Sci U S A ; 104(7): 2068-73, 2007 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-17287350

RESUMO

We have studied a naturally occurring small-molecule antimitotic called diazonamide A. Diazonamide A is highly effective at blocking spindle assembly in mammalian cell culture and does so through a unique mechanism. A biotinylated form of diazonamide A affinity purifies ornithine delta-amino transferase (OAT), a mitochondrial enzyme, from HeLa cell and Xenopus egg extracts. In the latter system, the interaction between diazonamide A and OAT is regulated by RanGTP. We find that specific OAT knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death, the effects largely phenocopying diazonamide A treatment in these cell lines. Our experiments reveal an unanticipated, paradoxical role for OAT in mitotic cell division and identify the protein as a target for chemotherapeutic drug development.


Assuntos
Divisão Celular/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Mitose/efeitos dos fármacos , Ornitina-Oxo-Ácido Transaminase/fisiologia , Oxazóis/farmacologia , Animais , Antimitóticos/farmacologia , Antineoplásicos , Morte Celular , Linhagem Celular Tumoral , Células HeLa , Humanos , Proteínas Mitocondriais/fisiologia , Oócitos , Ornitina-Oxo-Ácido Transaminase/genética , RNA Interferente Pequeno/farmacologia , Moduladores de Tubulina/farmacologia , Xenopus
14.
Dev Cell ; 8(2): 267-78, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15691767

RESUMO

Hedgehog (Hh) proteins control animal development by regulating the Gli/Ci family of transcription factors. In Drosophila, Hh counteracts phosphorylation by PKA, GSK3, and CKI to prevent Cubitus interruptus (Ci) processing through unknown mechanisms. Here, we show that these kinases physically interact with the kinesin-like protein Costal2 (Cos2) to control Ci processing and that Hh inhibits such interaction. Cos2 is required for Ci phosphorylation in vivo, and Cos2-immunocomplexes (Cos2IPs) phosphorylate Ci and contain PKA, GSK3, and CKI. By using a Kinesin-Cos2 chimeric protein that carries Cos2-interacting proteins to the microtubule plus end, we demonstrated that these kinases bind Cos2 in intact cells. PKA, GSK3, and CKI directly bind the N- and C-terminal regions of Cos2, both of which are essential for Ci processing. Finally, we showed that Hh signaling inhibits Cos2-kinase complex formation. We propose that Cos2 recruits multiple kinases to efficiently phosphorylate Ci and that Hh inhibits Ci phosphorylation by specifically interfering with kinase recruitment.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Cinesinas/metabolismo , Animais , Animais Geneticamente Modificados , Sítios de Ligação , Caseína Quinase I/genética , Caseína Quinase I/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas de Ligação a DNA/genética , Drosophila/genética , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Genes de Insetos , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Hedgehog , Cinesinas/química , Cinesinas/genética , Modelos Biológicos , Mutação , Fenótipo , Fosforilação , Processamento de Proteína Pós-Traducional , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Transcrição , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismo
15.
Dev Biol ; 268(2): 493-505, 2004 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-15063184

RESUMO

The Hedgehog (Hh) family of secreted proteins governs many developmental processes in both vertebrates and invertebrates. In Drosophila, Hh acts by blocking the formation of a truncated repressor form of Cubitus interruptus (Ci) and by stimulating the nuclear translocation and activity of full-length Ci (Ci155). In the absence of Hh, Ci155 is sequestered in the cytoplasm by forming protein complexes with Costal2 (Cos2), Fused (Fu) and Suppressor of Fused [Su(fu)]. How complex formation regulates Ci155 subcellular localization is not clear. We find that Cos2 interacts with two distinct domains of Ci155, an amino (N)-terminal domain (CDN) and a carboxyl (C)-terminal domain (CORD), and Cos2 competes with Su(fu) for binding to the N-terminal region of Ci155. We provide evidence that both N- and C-terminal Cos2 binding domains are involved in the cytoplasmic retention of Ci155 in imaginal discs. Treating imaginal discs with microtubule-destabilizing reagent nocodazole promotes nuclear translocation of Ci155, suggesting that the microtubule network plays an important role in the cytoplasmic retention of Ci155. In addition, we find that adding a nuclear localization signal (NLS) to exposed regions of Ci155 greatly facilitates its nuclear translocation, suggesting that the cytoplasmic retention of Ci155 may also depend on NLS masking.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Cinesinas/metabolismo , Microtúbulos/metabolismo , Animais , Citoplasma/metabolismo , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Larva/crescimento & desenvolvimento , Larva/metabolismo , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Estrutura Terciária de Proteína , Fatores de Transcrição
16.
Nature ; 416(6880): 548-52, 2002 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-11912487

RESUMO

The Drosophila protein Shaggy (Sgg, also known as Zeste-white3, Zw3) and its vertebrate orthologue glycogen synthase kinase 3 (GSK3) are inhibitory components of the Wingless (Wg) and Wnt pathways. Here we show that Sgg is also a negative regulator in the Hedgehog (Hh) pathway. In Drosophila, Hh acts both by blocking the proteolytic processing of full-length Cubitus interruptus, Ci (Ci155), to generate a truncated repressor form (Ci75), and by stimulating the activity of accumulated Ci155 (refs 2-6). Loss of sgg gene function results in a cell-autonomous accumulation of high levels of Ci155 and the ectopic expression of Hh-responsive genes including decapentaplegic (dpp) and wg. Simultaneous removal of sgg and Suppressor of fused, Su(fu), results in wing duplications similar to those caused by ectopic Hh signalling. Ci is phosphorylated by GSK3 after a primed phosphorylation by protein kinase A (PKA), and mutating GSK3-phosphorylation sites in Ci blocks its processing and prevents the production of the repressor form. We propose that Sgg/GSK3 acts in conjunction with PKA to cause hyperphosphorylation of Ci, which targets it for proteolytic processing, and that Hh opposes Ci proteolysis by promoting its dephosphorylation.


Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/fisiologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais , Sequência de Aminoácidos , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas de Ligação a DNA/genética , Inibidores Enzimáticos , Quinase 3 da Glicogênio Sintase , Quinases da Glicogênio Sintase , Proteínas Hedgehog , Dados de Sequência Molecular , Mutação , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/fisiologia , Fatores de Transcrição , Xenopus
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...