• Title/Summary/Keyword: p21 protein

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Expression of p21, p27 in Osteosarcoma and Its Prognostic Significance (p21, p27 단백질의 발현과 골육종 예후와의 관련성)

  • Oh, Joo-Han;Lee, Sang-Hoon;Cho, Whan-Seong;Yoo, Kwang-Hyun;Kim, Jin-Sam;Gong, Hyun-Sik;Suh, Sung-Wook;Kim, Ji-Eun;Kim, Han-Soo
    • The Journal of the Korean bone and joint tumor society
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    • v.9 no.2
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    • pp.169-177
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    • 2003
  • Purpose: The purpose of the current study is to evaluate the correlation between the expressions of p21 and p27 in osteosarcoma, and prognostic impact such as local recurrence, distant metastasis and survival rate. Materials and methods: Between 1988 and 2001, forty patients who underwent surgery, followed more than 12 months, and whose pathologic blocks were available, were evaluated retrospectively. Their formalin-fixed and paraffin-embedded tumor specimens were investigated. The correlation between expressions of p21, p27, local recurrence, distant metastasis and survival rate was statistically evaluated. Results: p21 protein was expressed in 38 (95%) patients. p27 protein was expressed in 14 (35%) patients. Patients with high expression of p21 had more frequent metastasis and poorer results (p=0.024). In contrast with these findings, patients with positive staining of the p27 had the significant lower distant metastasis (p=0.028). Conclusion: The prognosis of the osteosarcoma according to the expression level of p21 and p27 had inverse relationship which had unknown mechanism. Further work will be needed to define the relationship between p21 and p27.

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$p19^{ras}$ Accelerates $p73{\beta}$-mediated Apoptosis through a Caspase-3 Dependent Pathway

  • Jang, Sang-Min;Kim, Jung-Woong;Choi, Kyung-Hee
    • Animal cells and systems
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    • v.13 no.4
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    • pp.399-403
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    • 2009
  • $p19^{ras}$ is an alternative splicing variant of the proto-oncogene c-H-ras pre-mRNA of $p21^{ras}$. In contrast to $p21^{ras}$, $p19^{ras}$ does not have a C-terminal CAAX motif that targets the plasma membrane and is localized to both the cytoplasm and nucleus. We found that $p19^{ras}$ activated the transcriptional activity of $p73{\beta}$ through protein-protein interactions in the nucleus. p73 is known to play an important role in cellular damage responses such as apoptosis. Although p73 is a structural and functional homologue of p53, p73-mediated apoptosis has not yet been clearly elucidated. In this study, we demonstrate that the interaction between $p19^{ras}$ and $p73{\beta}$ accelerated $p73{\beta}$-induced apoptosis through a caspase-3 dependent pathway. Treatment with DEVD-CHO, a caspase inhibitor, also strengthened $p73{\beta}$-mediated apoptosis through a caspase-3 dependent pathway. Furthermore, the enhanced transcriptional activity of endogenous $p73{\beta}$ by treatment with Taxol was amplified by $p19^{ras}$ overexpression, which markedly increased caspase-3 dependent apoptosis in the p53-null SAOS2 cancer cell line. Our findings indicate a functional linkage between $p19^{ras}$ and p73 in caspase-3 mediated apoptosis of cancer cells.

The Overview of the Importances of Tumor Suppressor p53 for Investigating Molecular Toxicological Mechanisms of Various Environmental Mutagens (다양한 환경변이원의 분자독성학적 메커니즘 연구에 있어서 항종양 인자 p53의 중요성 고찰)

  • Jung Hwa Jin;Ryu Jae-Chun;Seo Young Rok
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.321-326
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    • 2004
  • The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.

Suppression of Human Prostate Cancer Cell Growth by β-Lapachone via Down-regulation of pRB Phosphorylation and Induction of Cdk Inhibitor p21WAF1/CIP1

  • Choi, Yung-Hyun;Kang, Ho-Sung;Yoo, Mi-Ae
    • BMB Reports
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    • v.36 no.2
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    • pp.223-229
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    • 2003
  • The product of a tree (Tabebuia avellanedae) from South America, $\beta$-lapachone, is known to exhibit various pharmacological properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which $\beta$-lapachone exerts its anti-proliferative action in cultured human prostate cancer cells. We observed that the proliferation-inhibitory effect of $\beta$-lapachone was due to the induction of apoptosis, which was confirmed by observing the morphological changes and cleavage of the poly(ADP-ribose) polymerase protein. A DNA flow cytometric analysis also revealed that $\beta$-lapachone arrested the cell cycle progression at the G1 phase. The effects were associated with the down-regulation of the phosphorylation of the retinoblastoma protein (pRB) as well as the enhanced binding of pRB and the transcription factor E2F-1. Also, $\beta$-lapachone suppressed the cyclindependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. Furthermore, this compound induced the levels of the Cdk inhibitor $p21^{WAF1/CIP1}$ expression in a p53-independent manner, and the p21 proteins that were induced by $\beta$-lapachone were associated with Cdk2. $\beta$-lapachone also activated the reporter construct of a p21 promoter. Overall, our results demonstrate a combined mechanism that involves the inhibition of pRB phosphorylation and induction of p21 as targets for $\beta$-lapachone. This may explain some of its anticancer effects.

A study of the Emulsifying Properties of Kidney Bean Protein Isolate (분리 강남콩 단백질의 유화특성에 관한 연구)

  • 최희령;손경희;민성희
    • Korean journal of food and cookery science
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    • v.5 no.2
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    • pp.9-17
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    • 1989
  • This study was carried out in order to study the emulsifying properties of kidney bean protein isolate. Kidney bean protein isolate was tested for the purpose of finding out the effect of pH, addition of NaCl, and heat treatment on the solbulity and emulsion capacity, emulsion stability, surface hydropobicity and emulsion viscosity. The results were summarized as follows. 1 The solubility of kidney bean protein isolate was affected by pH and showed the lowest value at pll 4.5 which is isoelectric point of kidney bean isolate. When the kidney bean protein isolate was heated, the highest value observed at pH 2 and pH 7 was 96.11%, 97.41% respectively. 2. The emulsion capacity of kidney bean protein isolate was not significantly different with each pH. With addition of NaCl, emulsion capacity decreased steadily. When heated thr highest value observed at pH 2 and pH 7 was 82.91 ml oil/100 mg protein ($60^{\circ}C$), 82.08 m1 oil/100 mg protein ($80^{\circ}C$) respectively. 3. The emulsion stability was significantly higher at pH 4.5 than that of pH 2 and pH 7 (p 0.05) When NaCl was added, emulsion stability was generally increased after 2hrs. When heated, the highest value observed at pH 2 and pH 7 was 21.25% ($80^{\circ}C$),23.7%($100^{\circ}C$) respectively after 2hrs. 4. Surface hydrophobicity increased sharply as 0.2 M NaCl was added to pH 4.5. When heated, the surface hydrophobicity increased as the temperature increased. 5. The highest value of emulsion viscosity was observed at pH 4.5 and pH 7 when 0.2 M NaCl was added. Under heat treatment, the highest value was 48,000 cps at pH 4.5 ($40^{\circ}C$). In the case of pH 7, the highest value was 105,000 cpa at $100^{\circ}C$.

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Mitogen-activated Protein Kinases in the Development of Normal and Diseased Kidneys

  • Awazu, Midori
    • Childhood Kidney Diseases
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    • v.21 no.1
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    • pp.1-7
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    • 2017
  • Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and $TGF-{\beta}1$ expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.

Effect of Protein Feeding Systems for Egg-type Growing Pullets on Pullet Growth, Nutrient Consumption and Subsequent Laying Performance (난용계 육성기의 단백질 공급체계가 육성계의 성장 및 영양소 섭취량과 산란능력에 미치는 영향)

  • 이규호;정연종
    • Korean Journal of Poultry Science
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    • v.21 no.4
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    • pp.257-266
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    • 1994
  • Three protein feeding systems for egg-type pullets involving conventional step-down protein 18-15-12%), step-up protein(12-15-18%) and single-stage low protein (13-13-13%) with an iso-energy level of 2,900 ME kcal /kg were compared to examine the effect on pullet growth and subsequent laying performance. During the growing period, pullets subjected to the step-up and single-stage low protein feeding systems were lighter in body weight and consumed less feed and netabolizable energy than those on the conventional step-down protein feeding system(P<0.05). 3ut the pullets on the step-up protein diet consumed more protein, and those on the single-stage low protein diet consumed less protein than those on the step-down protein diet(P<0.05). Also, he feed cost was less in pullets on the single-stage low protein diet than in those on the other systems(P<0.05). During the laying period, sexual maturity was later in hens reared on the step-up and single-stage low protein diets than in those on the step-down protein diet(P<0.05), however, average hen-day egg production and egg weight were not significantly affected by the protein feeding systems in the growing period. Daily feed intake and feed required per egg were significantly reduced in hens on the single-stage low protein diet compared to those on conventional protein feeding system(P<0.05). It was concluded that the 13% single-stage low protein feeding system produced smaller pullets with less feed, energy, protein, and feed cost during the growing period, and hens reared on that system consumed less feed during the laying period without any impairment of production compared to the conventional rearing system.

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Metabolic Syndrome Risk by Intake Ratio and Intake Pattern of Proteins in Middle-aged Men Based on the 2012-2013 Korean National Health and Nutrition Examination Survey Data (2012년~2013년 국민건강영양조사 자료를 이용한 중년 남성의 단백질섭취비와 섭취패턴에 따른 대사증후군 위험도 비교)

  • Jang, Minkyoung;Her, Eunsil;Lee, Kyunghea
    • Korean Journal of Community Nutrition
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    • v.21 no.4
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    • pp.366-377
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    • 2016
  • Objectives: The purpose of the study was to compare intake of energy nutrients, physical characteristics, and the prevalence of metabolic syndrome according to protein intake group. Methods: Subjects were 827 men aged 40-65 years. The results presented were based on data from the 2012-2013 National Health and Nutrition Examination Survey and analyzed using SPSS. The odds ratio (OR) of metabolic syndrome was assessed according to the protein intake group and intake pattern of protein-rich foods. Results: The mean of protein intake was $73.96{\pm}0.71g$. According to level of protein intake, four groups (deficient, normal, excess 1, excess 2) were created and their percentages were 8.3%, 39.6%, 37.1%, and 15.0% respectively. The mean of daily energy intake was $2,312.33{\pm}24.08kcal$. It was higher in excess group 2 than in the deficiency group (p < 0.001). Moreover, the intake of all energy nutrients increased significantly with protein intake group (p < 0.001). The main contribution to daily protein included mixed grains ($10.96{\pm}0.32g$), milled rice ($7.14{\pm}0.30g$), chicken ($3.50{\pm}0.21g$), and grilled pork belly ($3.04{\pm}0.16g$). With regard to physical characteristics, and blood pressure and blood test results, only body mass index increased significantly according to protein intake groups (p < 0.05). The prevalence of metabolic syndrome in subjects was 38.5%, and there was no significant correlation with protein intake group. The OR of metabolic syndrome increased with protein intake, and was higher 4.452 times in excess group 2 than in the normal group (p < 0.05). Conversely, the OR of metabolic syndrome according to the frequency of protein-rich food intake did not show a significant correlation. Conclusions: The results of this study can be used as significant supporting data to establish guidelines for protein intake in middle-aged men.

Cell Death Mediated by Vibrio parahaemolyticus Type III Secretion System 1 Is Dependent on ERK1/2 MAPK, but Independent of Caspases

  • Yang, Yu-Jin;Lee, Na-Kyung;Lee, Na-Yeon;Lee, Jong-Woong;Park, Soon-Jung
    • Journal of Microbiology and Biotechnology
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    • v.21 no.9
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    • pp.903-913
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    • 2011
  • Vibrio parahaemolyticus, which causes gastroenteritis, wound infection, and septicemia, has two sets of type III secretion systems (TTSS), TTSS1 and TTSS2. A TTSS1-deficient vcrD1 mutant of V. parahaemolyticus showed an attenuated cytotoxicity against HEp-2 cells, and a significant reduction in mouse lethality, which were both restored by complementation with the intact vcrD1 gene. V. parahaemolyticus also triggered phosphorylation of mitogen-activated protein kinases (MAPKs) including p38 and ERK1/2 in HEp-2 cells. The ability to activate p38 and ERK1/2 was significantly affected in a TTSS1-deficient vcrD1 mutant. Experiments using MAPK inhibitors showed that p38 and ERK1/2 MAPKs are involved in V. parahaemolyticus-induced death of HEp-2 cells. In addition, caspase-3 and caspase-9 were processed into active forms in V. parahaemolyticus-exposed HEp-2 cells, but activation of caspases was not essential for V. parahaemolyticus-induced death of HEp-2 cells, as shown by both annexin V staining and lactate dehydrogenase release assays. We conclude that secreted protein(s) of TTSS1 play an important role in activation of p38 and ERK1/2 in HEp-2 cells that eventually leads to cell death via a caspase-independent mechanism.

Construction of a Novel Shuttle Vector for Tetragenococcus species based on a Cryptic Plasmid from Tetragenococcus halophilus

  • Min Jae Kim;Tae Jin Kim;Yun Ji Kang;Ji Yeon Yoo;Jeong Hwan Kim
    • Journal of Microbiology and Biotechnology
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    • v.33 no.2
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    • pp.211-218
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    • 2023
  • A cryptic plasmid (pTH32) was characterized from Tetragenococcus halophilus 32, an isolate from jeotgal, Korean traditional fermented seafood. pTH32 is 3,198 bp in size with G+C content of 35.84%, and contains 4 open reading frames (ORFs). orf1 and orf2 are 456 bp and 273 bp in size, respectively, and their translation products showed 65.16% and 69.35% similarities with RepB family plasmid replication initiators, respectively, suggesting the rolling-circle replication (RCR) mode of pTH32. orf3 and orf4 encodes putative hypothetical protein of 186 and 76 amino acids, respectively. A novel Tetragenococcus-Escherichia coli shuttle vector, pMJ32E (7.3 kb, Emr), was constructed by ligation of pTH32 with pBluescript II KS(+) and an erythromycin resistance gene (ErmC). pMJ32E successfully replicated in Enterococcus faecalis 29212 and T. halophilus 31 but not in other LAB species. A pepA gene, encoding aminopeptidase A (PepA) from T. halophilus CY54, was successfully expressed in T. halophilus 31 using pMJ32E. The transformant (TF) showed higher PepA activity (49.8 U/mg protein) than T. halophilus 31 cell (control). When T. halophilus 31 TF was subculturd in MRS broth without antibiotic at 48 h intervals, 53.8% of cells retained pMJ32E after 96 h, and only 2.4% of cells retained pMJ32E after 14 days, supporting the RCR mode of pTH32. pMJ32E could be useful for the genetic engineering of Tetragenococcus and Enterococcus species.