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1.
PLoS One ; 2(10): e1076, 2007 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-17957258

RESUMO

BACKGROUND: NIMA-related kinases (Neks) have been studied in diverse eukaryotes, including the fungus Aspergillus and the ciliate Tetrahymena. In the former, a single Nek plays an essential role in cell cycle regulation; in the latter, which has more than 30 Neks in its genome, multiple Neks regulate ciliary length. Mammalian genomes encode an intermediate number of Neks, several of which are reported to play roles in cell cycle regulation and/or localize to centrosomes. Previously, we reported that organisms with cilia typically have more Neks than organisms without cilia, but were unable to establish the evolutionary history of the gene family. METHODOLOGY/PRINCIPLE FINDINGS: We have performed a large-scale analysis of the Nek family using Bayesian techniques, including tests of alternate topologies. We find that the Nek family had already expanded in the last common ancestor of eukaryotes, a ciliated cell which likely expressed at least five Neks. We suggest that Neks played an important role in the common ancestor in regulating cilia, centrioles, and centrosomes with respect to mitotic entry, and that this role continues today in organisms with cilia. Organisms that lack cilia generally show a reduction in the number of Nek clades represented, sometimes associated with lineage specific expansion of a single clade, as has occurred in the plants. CONCLUSION/SIGNIFICANCE: This is the first rigorous phylogenetic analysis of a kinase family across a broad array of phyla. Our findings provide a coherent framework for the study of Neks and their roles in coordinating cilia and cell cycle progression.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Cílios/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Teorema de Bayes , Ciclo Celular , Evolução Molecular , Genoma , Humanos , Quinase 1 Relacionada a NIMA , Fosforilação , Fosfotransferases/química , Filogenia , Transdução de Sinais , Software , Tetrahymena
2.
Proc Natl Acad Sci U S A ; 104(44): 17524-9, 2007 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-17959775

RESUMO

Reception and interpretation of environmental stimuli is critical for the survival of all organisms. Here, we show that the ablation of BBS1 and BBS4, two genes mutated in Bardet-Biedl syndrome and that encode proteins that localize near the centrioles of sensory neurons, leads to alterations of s.c. sensory innervation and trafficking of the thermosensory channel TRPV1 and the mechanosensory channel STOML3, with concomitant defects in peripheral thermosensation and mechanosensation. The thermosensory phenotype is recapitulated in Caenorhabditis elegans, because BBS mutants manifest deficient thermosensory responses at both physiological and nociceptive temperatures and defective trafficking of OSM-9, a polymodal sensory channel protein and a functional homolog of TRPV1 or TRPV4. Our findings suggest a hitherto unrecognized, but essential, role for mammalian basal body proteins in the acquisition of mechano- and thermosensory stimuli and highlight potentially clinical features of ciliopathies in humans.


Assuntos
Sistema Nervoso Central/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Adolescente , Adulto , Animais , Animais Geneticamente Modificados , Síndrome de Bardet-Biedl/metabolismo , Síndrome de Bardet-Biedl/patologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Microscopia Eletrônica , Mutação/genética , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Fenótipo , Temperatura
3.
J Cell Sci ; 118(Pt 15): 3317-26, 2005 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16030138

RESUMO

The cycle of ciliogenesis and ciliary disassembly is coordinated with cell division. In the unicellular alga Chlamydomonas, the two flagella are maintained at constant and equal length during interphase, and are reabsorbed prior to mitosis. We report that the NIMA-related kinase, Cnk2p, is an axonemal protein that affects flagellar length via effects on disassembly rate and also plays a role in the cellular assessment of size prior to committing to mitosis. This is the second NIMA-related kinase shown to affect ciliary function and cell cycle progression in Chlamydomonas. We speculate that members of the NIMA family have evolved nuanced roles to coordinate cilia/cell cycle regulation.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Tamanho Celular , Chlamydomonas reinhardtii/citologia , Chlamydomonas reinhardtii/enzimologia , Flagelos/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/fisiologia , Regulação Enzimológica da Expressão Gênica , Mitose/fisiologia , Quinase 1 Relacionada a NIMA , Proteínas de Plantas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , RNA Interferente Pequeno/genética
4.
J Eukaryot Microbiol ; 51(1): 66-72, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15068267

RESUMO

The NIMA kinases are an evolutionarily conserved protein family with enigmatic roles in the regulation of mitosis. We report six new members of this family in Chlamydomonas, in addition to the previously identified NIMA-related kinase, Fa2p. Chlamydomonas NIMA-related kinases (CNKs) 1-6 were sequenced from subclones generated by RT-PCR using information from EST libraries and the recently sequenced Chlamydomonas genome. Phylogenetic and bioinformatic approaches were used to determine the relationships of the six new members with known members of the NIMA-related kinase family. Although humans express at least eleven NIMA-related kinases, the eukaryotic microbes that have been studied to date express only one or two members of the family. Thus, the discovery that Chlamydomonas expresses a total of at least seven NIMA-related kinases is intriguing. Our analyses suggest that members of this family may play roles in the assembly and function of cilia.


Assuntos
Proteínas de Ciclo Celular/genética , Chlamydomonas/genética , Proteínas Serina-Treonina Quinases/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Chlamydomonas/classificação , Chlamydomonas/enzimologia , Sequência Conservada , Primers do DNA , Regulação Enzimológica da Expressão Gênica , Dados de Sequência Molecular , Quinase 1 Relacionada a NIMA , Filogenia , Proteínas de Protozoários/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
5.
World J Urol ; 20(3): 167-74, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12196900

RESUMO

Radical cystectomy with pelvic lymph node dissection has been accepted as the standard treatment for muscle-invasive bladder cancer. Radiation therapy and chemotherapy are increasingly being implemented in bladder-preservation protocols to provide an alternative treatment to cystectomy. We review experience with radiation and chemotherapy in treating bladder cancer and their use in bladder-preservation protocols. Multimodality organ-sparing treatment strategies offer overall survival rates comparable to radical cystectomy and pelvic lymph node dissection in selected cases. However, bladder-preservation techniques risk local recurrence of potentially aggressive tumors whose long-term effect on cancer-specific survival has not been fully characterized. No improvement in quality of life has clearly been demonstrated with bladder-preservation regimens. Bladder-preservation protocols are costly and require precise coordination of multiple specialists as well as strict, life-long patient compliance. Bladder-preservation protocols should only be performed at tertiary care centers with experience in their administration and be limited to patients desiring an alternative cystectomy or who are not surgical candidates.


Assuntos
Tratamento Farmacológico , Músculos/patologia , Radioterapia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Humanos
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