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1.
Medicine (Baltimore) ; 101(40): e30733, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36221388

RESUMO

RATIONALE: Diagnosing multifactorial, multidimensional symptoms unexplained by presumptive diagnosis is often challenging for infectious disease specialists. PATIENT CONCERNS: We report a rare case of a 30-year-old Japanese bisexual man with a history of virally suppressed human immunodeficiency virus and syphilis infections who developed chest pain and an erosive lesion under the lower midline jaw. DIAGNOSIS: Imaging examinations revealed erosive lesions on the sternum and left the ninth rib. Biopsy and polymerase chain reaction testing of sternal tissue specimens were noncontributory. However, due to elevated rapid plasma regain levels, a diagnosis of syphilitic osteomyelitis and gumma of the jaw was made. INTERVENTIONS: The patient was treated with 5 weeks of intravenous ceftriaxone and then with 8 weeks of oral amoxicillin. OUTCOME: After the antibiotic treatment, bone pain disappeared. We conducted a literature review on syphilitic osteomyelitis, and all of the articles included were case reports. Approximately half of the 46 patients with syphilitic osteomyelitis had HIV coinfection, and 10 (22%) patients lacked signs of early syphilis. Given its rarity, clinical data to establish appropriate guidelines for diagnosing and treating syphilitic osteomyelitis are still lacking. Cognitive biases, such as anchoring, cognitive overload bias, and premature closure, may contribute to diagnostic delays. LESSONS: In cases of idiopathic multiple bone lesions, syphilis must always be ruled out, and clinicians should guard against cognitive pitfalls when diagnosing rare diseases.


Assuntos
Infecções por HIV , Osteomielite , Sífilis , Adulto , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Viés , Ceftriaxona/uso terapêutico , Raciocínio Clínico , Cognição , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Osteomielite/complicações , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico
2.
J Gastrointest Oncol ; 13(3): 1384-1394, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35837184

RESUMO

Background: The human chorionic gonadotropin free beta-subunit (hCGß) is ectopically produced in various epithelial cancers and is associated with poor prognoses. However, its molecular mechanism remains unclear. In this study, we examined the biological role of hCGß in pancreatic cancer progression. Methods: Tissue specimens of 30 patients with pancreatic cancer were examined immunohistochemically to investigate the relationship between hCGß expression and clinicopathological features. We also evaluated the molecular effects of hCGß-downregulated pancreatic cell lines. Results: Total of 21 cases were positive for immunostaining, and 17 of 25 metastatic lymph nodes were positive. hCGß expression levels were correlated with pancreatic cancer T and N factors. hCGß expression was significantly associated with poor overall and recurrence-free survival (P<0.001). In a multivariate analysis, hCGß expression was independently associated with overall survival (HR 14.0; 95% CI: 1.5-130; P=0.019). The proliferative, invasive, and migratory abilities of hCGß-downregulated cell lines were reduced compared with the control cell lines. Moreover, downregulation of hCGß reduced vimentin, slug, and α-smooth muscle actin expression and increased E-cadherin expression. Conclusions: hCGß expression is related to cancer progression and poor prognoses via epithelial mesenchymal transition. hCGß is a potential prognostic marker and molecular target in pancreatic cancer.

3.
Biochem Biophys Rep ; 30: 101233, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35243014

RESUMO

Ameloblastoma is an odontogenic tumor located in the bone jaw with clinical characteristics of extensive bone resorption. It is a locally invasive tumor with a high recurrence rate despite adequate surgical removal. In bone disease, tumors and other cells including osteoblasts, osteoclasts, and osteocytes in the bone microenvironment contribute to the pathogenesis of tumor growth. However, the effect of osteoblasts on ameloblastoma cells is not well-understood, and there has been limited research on interactions between them. This study investigated interactions between ameloblastoma cells and osteoblasts using a human ameloblastoma cell line (AM-3 ameloblastoma cells) and a murine pre-osteoblast cell line (MC3T3-E1 cells). We treated each cell type with the conditioned medium by the other cell type. We analyzed the effect on cytokine production by MC3T3-E1 cells and the production of MMPs by AM-3 cells. Treatment with AM-3-conditioned medium induced inflammatory cytokine production of IL-6, MCP-1, and RANTES from MC3T3-E1 cells. The use of an IL-1 receptor antagonist suppressed the production of these inflammatory cytokines by MC3T3-E1 cells stimulated with AM-3-conditioned medium. The MC3T3-E1-conditioned medium triggered the expression of MMP-2 from AM-3 cells. Furthermore, we have shown that the proliferation and migration activity of AM-3 cells were accelerated by MC3T3-E1 conditioned media. In conclusion, these intercellular signalings between ameloblastoma cells and osteoblasts may play multiple roles in the pathogenesis of ameloblastoma.

4.
FEBS Open Bio ; 7(12): 2000-2007, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29226086

RESUMO

Ameloblastoma is a benign tumor of the odontogenic epithelium with several histological subtypes. All subtypes of ameloblastoma contain abundant stroma; the tumor cells invade collectively into the surrounding tissues without losing intratumor cell attachments. However, the molecular mechanisms mediating ameloblastoma invasion remain unclear. Here, we evaluated the functional significance of the interactions between ameloblastoma tumor cells and stromal fibroblasts on collective cellular invasion using a three-dimensional cultivation method, double-layered collagen gel hemisphere (DL-CGH) culture. The AM-1 plexiform and AM-3 follicular human ameloblastoma cell lines and HFF-2 human fibroblasts were labeled with GFP and DsRed, respectively. Collective cellular invasion of ameloblastoma cells was assessed in the presence or absence of fibroblasts. Notably, without fibroblasts, AM-1 cells formed sharp, plexiform-like invasive processes, whereas AM-3 cells formed a series of blunt processes often observed during collective migration. In comparison, under the cocultures with HFF-2 fibroblasts, AM-3 cells formed tuft-like invasive processes and collectively invaded into outer layer more than that observed with AM-1 cells. Moreover, HFF-2 fibroblasts localized to the tips of the invasive tumor processes. These findings suggest that tumor-associated cells assist tumor cell invasion. Microscopic analysis of sectioned three-dimensional cultures revealed that AM-3/HFF-2 hemispheres were histologically similar to follicular ameloblastoma tumor samples. Therefore, our findings suggest that ameloblastoma subtypes exhibit distinct invasion patterns and that fibroblasts promote collective tumor invasion in follicular ameloblastoma.

5.
Sci Rep ; 5: 10536, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26030277

RESUMO

Wnt5a, which regulates various cellular functions in Wnt signaling, is involved in inflammatory responses, however the mechanism is not well understood. We examined the role of Wnt5a signaling in intestinal immunity using conditional knockout mice for Wnt5a and its receptor Ror2. Removing Wnt5a or Ror2 in adult mice suppressed dextran sodium sulfate (DSS)-induced colitis. It also attenuated the DSS-dependent increase in inflammatory cytokine production and decreased interferon-γ (IFN-γ)-producing CD4(+) Th1 cell numbers in the colon. Wnt5a was highly expressed in stromal fibroblasts in ulcerative lesions in the DSS-treated mice and inflammatory bowel disease patients. Dendritic cells (DCs) isolated from the colon of Wnt5a and Ror2 deficient mice reduced the ability to differentiate naïve CD4(+) T cells to IFN-γ-producing CD4(+) Th1 cells. In vitro experiments demonstrated that the Wnt5a-Ror2 signaling axis augmented the DCs priming effect of IFN-γ, leading to enhanced lipopolysaccharide (LPS)-induced interleukin (IL)-12 expression. Taken together, these results suggest that Wnt5a promotes IFN-γ signaling, leading to IL-12 expression in DCs, and thereby inducing Th1 differentiation in colitis.


Assuntos
Colite/metabolismo , Interferon gama/metabolismo , Interleucina-12/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , Animais , Medula Óssea/metabolismo , Colite/induzido quimicamente , Colite/genética , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças , Fibroblastos/metabolismo , Expressão Gênica , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout , Especificidade de Órgãos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Proteínas Wnt/genética , Proteína Wnt-5a
6.
PLoS One ; 9(11): e112900, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25390333

RESUMO

Werner syndrome (WS) is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs). In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.


Assuntos
Reprogramação Celular/genética , Senescência Celular/genética , Instabilidade Cromossômica/genética , Telômero/genética , Síndrome de Werner/genética , Adulto , Senilidade Prematura/genética , Senilidade Prematura/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação/genética , Neoplasias/genética , Fenótipo , Telomerase/metabolismo , Síndrome de Werner/metabolismo
7.
Biochem Biophys Res Commun ; 451(4): 491-6, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25124663

RESUMO

Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas.


Assuntos
Ameloblastoma/fisiopatologia , Comunicação Celular/fisiologia , Interleucina-1alfa/farmacologia , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Células Estromais/fisiologia , Linhagem Celular Tumoral , Humanos , Neoplasias Maxilomandibulares/fisiopatologia , Receptores de Interleucina-1/antagonistas & inibidores
8.
J Biochem ; 156(1): 29-38, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24621529

RESUMO

Glioblastoma is characterized by marked invasiveness, but little is known about the mechanism of invasion in glioblastoma cells. Wnts are secreted ligands that regulate cell proliferation, differentiation, motility and fate at various developmental stages. In adults, misregulation of the Wnt pathway is associated with several diseases. Recently, we reported that Wnt-5a was overexpressed and correlated with cell motility and infiltrative activity through the regulation of matrix metalloproteinase (MMP)-2 in glioma-derived cells. Although several receptors for Wnt-5a were identified, the receptors of Wnt-5a that mediate cellular responses of glioma were not clearly identified. Knockdown of receptor-like tyrosine kinase (Ryk) but not that of Ror2 suppressed the activity of MMP-2 and Wnt-5a-dependent invasive activity in glioma cells. These results suggest that Ryk is important for the Wnt-5a-dependent induction of MMP-2 and invasive activity in glioma-derived cells and that Ryk might have a novel patho-physiological function in adult cancer invasion. Furthermore, not only the expression of Wnt-5a but also that of Frizzled (Fz)-2 and Ryk was correlated with the WHO histological grade in 38 human glioma tissues. Taking these findings together, Fz-2 and Ryk could be therapeutic or pharmacological target molecules for the control of Wnt-5a-dependent invasion of human glioma in the near future.


Assuntos
Glioma/metabolismo , Glioma/patologia , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Proteínas Wnt/metabolismo , Linhagem Celular , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Invasividade Neoplásica , Receptores Proteína Tirosina Quinases/genética , Proteína Wnt-5a
9.
Int J Mol Sci ; 14(6): 10998-1010, 2013 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-23708100

RESUMO

Oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD) enzymes play a major role in the antioxidant system and they also catalyze superoxide radicals (O2·-). Since the loss of cytoplasmic SOD (SOD1) resulted in aging-like phenotypes in several types of mouse tissue, SOD1 is essential for the maintenance of tissue homeostasis. To clarify the cellular function of SOD1, we investigated the cellular phenotypes of Sod1-deficient fibroblasts. We demonstrated that Sod1 deficiency impaired proliferation and induced apoptosis associated with O2·- accumulation in the cytoplasm and mitochondria in fibroblasts. Sod1 loss also decreased the mitochondrial membrane potential and led to DNA damage-mediated p53 activation. Antioxidant treatments effectively improved the cellular phenotypes through suppression of both intracellular O2·- accumulation and p53 activation in Sod1-deficient fibroblasts. In vivo experiments revealed that transdermal treatment with a vitamin C derivative significantly reversed the skin thinning commonly associated with the upregulated p53 action in the skin. Our findings revealed that intrinsic O2·- accumulation promoted p53-mediated growth arrest and apoptosis as well as mitochondrial disfunction in the fibroblasts.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Superóxido Dismutase/deficiência , Superóxidos/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Atrofia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Derme/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fenótipo , Superóxido Dismutase/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Molecules ; 18(2): 1383-93, 2013 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-23348992

RESUMO

Redox imbalance elevates the reactive oxygen species (ROS) level in cells and promotes age-related diseases. Superoxide dismutases (SODs) are antioxidative enzymes that catalyze the degradation of ROS. There are three SOD isoforms: SOD1/CuZn-SOD, SOD2/Mn-SOD, and SOD3/EC-SOD. SOD2, which is localized in the mitochondria, is an essential enzyme required for mouse survival, and systemic knockout causes neonatal lethality in mice. To investigate the physiological function of SOD2 in adult mice, we generated a conditional Sod2 knockout mouse using a Cre-loxP system. When Sod2 was specifically deleted in the heart and muscle, all mice exhibited dilated cardiomyopathy (DCM) and died by six months of age. On the other hand, when Sod2 was specifically deleted in the skeletal muscle, mice showed severe exercise disturbance without morphological abnormalities. These provide useful model of DCM and muscle fatigue. In this review, we summarize the impact of antioxidants, which were able to regulate mitochondrial superoxide generation and improve the phenotypes of the DCM and the muscle fatigue in mice.


Assuntos
Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/fisiopatologia , Mitocôndrias/enzimologia , Fadiga Muscular/efeitos dos fármacos , Superóxido Dismutase/deficiência , Animais , Cardiomiopatia Dilatada/patologia , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Fenótipo
11.
EMBO J ; 29(1): 41-54, 2010 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-19910923

RESUMO

Wnt5a regulates multiple intracellular signalling cascades, but how Wnt5a determines the specificity of these pathways is not well understood. This study examined whether the internalization of Wnt receptors affects the ability of Wnt5a to regulate its signalling pathways. Wnt5a activated Rac in the beta-catenin-independent pathway, and Frizzled2 (Fz2) and Ror1 or Ror2 were required for this action. Fz2 was internalized through a clathrin-mediated route in response to Wnt5a, and inhibition of clathrin-dependent internalization suppressed the ability of Wnt5a to activate Rac. As another action of Wnt5a, it inhibited Wnt3a-dependent lipoprotein receptor-related protein 6 (LRP6) phosphorylation and beta-catenin accumulation. Wnt3a-dependent phosphorylation of LRP6 was enhanced in Wnt5a knockout embryonic fibroblasts. Fz2 was also required for the Wnt3a-dependent accumulation of beta-catenin, and Wnt5a competed with Wnt3a for binding to Fz2 in vitro and in intact cells, thereby inhibiting the beta-catenin pathway. This inhibitory action of Wnt5a was not affected by the impairment of clathrin-dependent internalization. These results suggest that Wnt5a regulates distinct pathways through receptor internalization-dependent and -independent mechanisms.


Assuntos
Receptores Frizzled/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Proteínas Wnt/metabolismo , Animais , Ligação Competitiva , Células CHO , Linhagem Celular , Clatrina/metabolismo , Cricetinae , Cricetulus , Células HeLa , Humanos , Células L , Proteínas Relacionadas a Receptor de LDL/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/farmacologia , RNA Interferente Pequeno/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Proteínas Wnt/antagonistas & inibidores , Proteínas Wnt/deficiência , Proteínas Wnt/genética , Proteínas Wnt/farmacologia , Proteína Wnt-5a , Proteína Wnt3 , Proteína Wnt3A , beta Catenina/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo
12.
J Biol Chem ; 282(22): 16465-75, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17428805

RESUMO

SUMO proteases possess two enzymatic activities to hydrolyze the C-terminal region of SUMOs (hydrolase activity) and to remove SUMO from SUMO-conjugated substrates (isopeptidase activity). SUMO proteases bind to SUMOs noncovalently, but the physiological roles of the binding in the functions of SUMO proteases are not well understood. In this study we found that SUMO proteases (Axam, SENP1, and yeast Ulp1) show different preferences for noncovalent binding to various SUMOs (SUMO-1, -2, -3, and yeast Smt3) and that the hydrolase and isopeptidase activities of SUMO proteases are dependent on their binding to SUMOs through salt bridge. Expression of Smt3 suppressed the phenotype of yeast mutant lacking smt3, which exhibits growth arrest, and the binding of Ulp1 to Smt3 was essential for this rescue activity. Although expression of an Smt3 mutant (smt3R64E(GG)), which conjugates to substrate but loses the ability to bind to Ulp1, rescued the phenotype of yeast lacking smt3 partially, the mutant cells showed an increment in the doubling time and a delay of desumoylation of Smt3-conjugated Cdc3. These results indicate that the noncovalent binding of SUMO protease to SUMO through salt bridge is essential for the enzymatic activities and that the balance between sumoylation and desumoylation is important for cell growth control.


Assuntos
Cisteína Endopeptidases/metabolismo , Endopeptidases/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Proteína SUMO-1/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cisteína Endopeptidases/genética , Endopeptidases/genética , Expressão Gênica , Humanos , Camundongos , Profilinas/genética , Profilinas/metabolismo , Ligação Proteica , Proteínas Recombinantes , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
13.
Biosci Biotechnol Biochem ; 68(4): 909-19, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15118322

RESUMO

RSC is a nucleosome-remodeling complex of Saccharomyces cerevisiae essential for growth that can alter histone-DNA interaction by using the energy of ATP hydrolysis. Nps1p/Sth1p is an ATPase subunit of RSC. A mutation in the conserved ATPase domain of Nps1p causes a sporulation defect with decreased expression of early meiotic genes, especially IME2. This defect is partially suppressed by the overexpression of either IME1 or IME2. A homozygous diploid of a novel temperature-sensitive nps1 mutation, nps1-13, harboring amino acid substitutions within the bromodomain, was unable to sporulate. Overexpression of IME, IME2, or both of these genes allowed the completion of meiosis I and meiosis II in nps1-13 but not the formation of mature asci. In nps1-13 carrying YEpIME1, the expression of a group of sporulation-specific genes, which express at the middle stages of sporulation and are required for spore-wall formation, notably diminished, and several late sporulation genes expressed at the early stages of sporulation. These results suggest that Nps1p/RSC plays important roles during the spore development process by controlling gene expression for initiating both meiosis and spore morphogenesis, and ensures proper expression timing of late meiotic genes.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Montagem e Desmontagem da Cromatina , Regulação Fúngica da Expressão Gênica , Proteínas Nucleares/metabolismo , Nucleossomos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Esporos Fúngicos/metabolismo , Transcrição Gênica/genética , Proteínas de Ciclo Celular/genética , Divisão Celular , Núcleo Celular/fisiologia , Diploide , Citometria de Fluxo , Genes Fúngicos/genética , Peptídeos e Proteínas de Sinalização Intracelular , Meiose/genética , Mutação/genética , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Nucleossomos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Esporos Fúngicos/citologia , Esporos Fúngicos/genética , Fatores de Transcrição/genética
14.
FEBS Lett ; 531(2): 215-21, 2002 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-12417315

RESUMO

The essential Nps1p/Sth1p is a catalytic subunit of the nucleosome-remodeling complex, RSC, of Saccharomyces cerevisiae that can alter nucleosome structure by using the energy of ATP hydrolysis. Besides the ATPase domain, Nps1p harbors the bromodomain, of which the function(s) have not yet been defined. We have isolated a temperature-sensitive mutant allele of NPS1, nps1-13, which has amino acid substitutions within the bromodomain. This mutation perturbed the interaction between the RSC components and enhanced the sensitivity of the cells to several DNA-damaging treatments at the permissive temperature. Reduced expression of NPS1 also caused DNA damage sensitivity. These results suggest the importance of the Nps1p bromodomain in RSC integrity and a model in which high amounts of RSC would be required for the cells to overcome DNA damage.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Dano ao DNA , Proteínas Fúngicas/fisiologia , Proteínas Nucleares , Nucleossomos/fisiologia , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Sequência Conservada , DNA Fúngico/análise , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Substâncias Macromoleculares , Mutação , Fenótipo , Estrutura Terciária de Proteína , Subunidades Proteicas , Saccharomyces cerevisiae/metabolismo , Temperatura
15.
FEMS Yeast Res ; 2(2): 87-91, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12702296

RESUMO

RSC, a for growth essential chromatin-remodeling complex of Saccharomyces cerevisiae, is composed of 15 subunits. Rsc1p and Rsc2p are highly homologous proteins and are contained in distinct RSC complexes. We found that both rsc1Delta and rsc2Delta homozygous diploids showed reduced sporulation with decreased expression of IME2 and that rsc1Delta, but not rsc2Delta, produced aberrant asci containing one to three spores. Overexpression of RSC2 in rsc1Delta recovered the sporulation efficiency but not the production of aberrant asci. In contrast, overexpression of RSC1 in rsc2Delta did not alleviate its sporulation defect. These results suggest that both Rsc1p and Rsc2p share overlapping functions on IME2 expression, with a prominent role for Rsc2p, whereas Rsc1p has an additional function in the late steps of the sporulation process.


Assuntos
Proteínas Cromossômicas não Histona/fisiologia , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/fisiologia , Esporos Fúngicos/fisiologia , Cromatina/fisiologia , Proteínas de Ligação a DNA/genética , Regulação Fúngica da Expressão Gênica , Meiose/genética , Saccharomyces cerevisiae/genética
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