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cdk2 nf-y

Kang Liu, Fang-Tsyr Lin, Joshua D Graves, Yu-Ju Lee, Weei-Chin Lin
Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
S-J Lee, Y H Jung, S Y Oh, E J Song, S H Choi, H J Han
The Gram-negative bacterium Vibrio vulnificus produces hemolysin (VvhA), which induces cytotoxicity in mammalian cells. However, our understanding of the cytotoxic mechanism and the modes of action of VvhA are still fragmentary and incomplete. The recombinant protein (r) VvhA (50 pg/ml) significantly induces necrotic cell death and apoptosis in human intestinal epithelial (INT-407) cells. The apoptotic cell death induced by rVvhA is highly susceptible to the sequestration of cholesterol by methyl-β-cyclodextrin, whereas for necrotic cell death, this shows a marginal effect...
2015: Cell Death & Disease
Suryatheja Ananthula, Parash Parajuli, Fathy A Behery, Alaadin Y Alayoubi, Khalid A El Sayed, Sami Nazzal, Paul W Sylvester
BACKGROUND: Oxazine derivatives of tocotrienols display enhanced anticancer activity. Studies were conducted to further characterize these effects in vivo. MATERIALS AND METHODS: Tetrazolium assay was used to determine the inhibitory effects of oxazine derivatives of γ-tocotrienol and δ-tocotrienol in vitro. These compounds were further formulated as lipid nanoemulsions and intralesional administration was used to examine their anticancer activity in vivo. RESULTS: Tocotrienol oxazine derivatives significantly inhibited +SA mammary tumor growth in syngeneic mice as compared to their respective parent compound, and these effects were associated with a reduction in cell proliferation and survival (phosphorylated protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and cyclooxygenase-2 (COX2) and cell-cycle progression (cyclin D1, cyclin-dependent kinase 2 (CDK2), CDK4 and CDK6) markers, and increase in cell-cycle arrest proteins (p21 and p27)...
June 2014: Anticancer Research
Y-C Lin, Y-N Chen, K-F Lin, F-F Wang, T-Y Chou, M-Y Chen
Polo-like kinase 1 (PLK1) is an important mitotic kinase and its expression is tightly regulated in the cell cycle and in the DNA damage response. PLK1 expression is previously shown to be suppressed by p53 and/or p21. Here, we demonstrate that the CCAAT box in the PLK1 promoter is pivotal for p53/p21-mediated PLK1 repression. Chromatin immunoprecipitation showed that cyclin-dependent kinase 2 (CDK2) associated with the CCAAT box-containing region of PLK1 promoter in unstressed cells, whereas adriamycin (ADR) induced the recruitment of p21 with a concomitant reduction in the occupancy of CDK2 in this region...
2014: Cell Death & Disease
Hee-Don Chae, Jungbin Kim, Deug Y Shin
We previously reported that CDK2/Cyclin A can phosphorylate and activate the transcription factor NF-Y. In this study, we investigated a potential regulatory role for NF-Y in the transcription of Cyclin A and other cell cycle regulatory genes. Gel-shift assays demonstrate that NF-Y binds to CCAAT sequences in the Cyclin A promoter, as well as to those in the promoters of cell cycle G2 regulators such as CDC2, Cyclin B and CDC25C. Furthermore, expression of Cyclin A increases NF-Y's affinity for CCAAT sequences in the CDC2 promoter; however, Cyclin A's induction of CDC2 transcription is antagonized by p21, an inhibitor of CDK2/Cyclin A...
August 2011: BMB Reports
Un-Jung Yun, Heui-Dong Park, Deug Y Shin
PURPOSE: Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and this function is required for the maintenance of genomic integrity. In this study, we addressed a role of p53 in escaping from cell cycle G2 arrest following DNA damage. MATERIALS AND METHODS: Cell cycle checkpoint arrest in the human colon cancer cell line HCT116 and its derivatives carry p53 or p21 deletions, were examined by FACS analysis, immunoprecipitation, Western blot and IP-kinase assay...
December 2006: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Hee Don Chae, Jeanho Yun, Deug Y Shin
NF-Y transcription factor binds to CCAAT boxes on promoters of cell cycle regulatory genes such as cdc2, cyclin B, cdc25C, and cyclin A. We previously reported that the DNA binding activity of NF-Y is regulated by p53-p21-cdk2 pathway. CBF/HSP70 was originally identified as a transcription factor binding to the CCAAT box on the hsp70 promoter and mediates transcription repression of hsp70 pro- moter by p53. Recently it was demonstrated that CBF/HSP70 interacts and cooperates with NF-Y. In this study, we found that p53 represses the trans-cription of CBF/HSP70...
October 31, 2005: Experimental & Molecular Medicine
Hee-Don Chae, Jeanho Yun, Yung-Jue Bang, Deug Y Shin
We previously reported that cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y transcription factor and this phosphorylation is essential for DNA binding of NF-Y. In this study, we examined the effects of a phosphorylation-deficient mutant form of YA, YA-aa, in which the two serine residues are replaced with alanine, on the cell cycle and expression of the NF-Y target genes. Transient transfection assays show that YA-aa inhibits transcription from the NF-Y target promoters, such as cdc2, cyclin A, and cdc25C...
May 20, 2004: Oncogene
Sanna Ryhänen, Tiina Jääskeläinen, Anitta Mahonen, Pekka H Mäenpää
Progression through eukaryotic cell division cycle is regulated by synergistic activities of both positive and negative regulatory factors. The active form of vitamin D(3) (1alpha,25(OH)(2)D(3), 1,25D) and a number of its synthetic analogs have been shown to arrest cells in the G(1) phase of the cell cycle. In the present study, 1alpha,25(OH)(2)D(3) and the analogs KH1060, EB1089, and CB1093 were used to study the mechanism of the cell cycle arrest and to compare the effectiveness of these compounds in human MG-63 osteosarcoma cells...
August 1, 2003: Biochemical Pharmacology
Jeanho Yun, Hee-Don Chae, Tae-Saeng Choi, Eun-Hee Kim, Yung-Jue Bang, Jongkyeong Chung, Kyeong-Sook Choi, Roberto Mantovani, Deug Y Shin
Recent studies have suggested that the NF-Y transcription factor is involved in transcription repression of the cell cycle regulatory genes in a response to p53 induction or DNA damage. Here we demonstrate the cdk2-dependent phosphorylation of NF-Y and its involvement in transcription repression by the p53-p21 signaling pathway. Cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y. Cyclin A-cdk2 appears to associate with NF-Y both in vitro and in vivo. Furthermore, YA protein is phosphorylated in parallel with a cell cycle-dependent activation of cdk2 kinase and cyclin A expression...
September 19, 2003: Journal of Biological Chemistry
Yisong Y Wan, James DeGregori
We have explored the interactions between the NFkappaB and Cdk-Rb-E2F pathways in controlling T cell fate following antigen stimulation. The inhibition of NFkappaB in antigen-stimulated T cells results in apoptosis but does not inhibit E2F activation and S phase entry. IkappaB-induced apoptosis coincides with the superinduction of p73 expression and activity. G1 Cdk activity is required for IkappaB-induced apoptosis and the induction of p73. Importantly, p73 deficiency rescues activated T cells from the apoptosis resulting from the inhibition of NFkappaB...
March 2003: Immunity
J T Hong, E J Kim, K S Ahn, K M Jung, Y P Yun, Y K Park, S H Lee
Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been used commonly as a cosmetic ingredient since it was discovered to have photoprotective and anti-inflammatory effects and antioxidant effects on ultraviolet (UV)B-irradiated skin. Little is known, however, about the functional role of glycolic acid on UV-induced skin tumorigenesis. In the present study, we examined the effect of glycolic acid on UV (UVA + UVB)-induced skin tumorigenesis and assessed several significant contributing factors in SKH-1 hairless mice...
July 2001: Molecular Carcinogenesis
Z F Chang, D Y Huang
As human diploid fibroblasts (HDFs) in culture senesce, the expression of thymidine kinase (TK) and the activity of its promoter become attenuated. Herein we analyze the cis-elements involved in transcriptional activation of the hTK promoter, and show that the Sp1 binding site located at -118/-113 and one CCAAT box located at either -71/-67 or -40/-36 are critical for maximal expression of hTK promoter activity in young IMR-90 HDFs. However, the DNA binding activities to TK-CCAAT and Sp1 were not defective in serum-stimulated senescent HDFs...
March 2001: Journal of Biomedical Science
Z F Chang, D Y Huang, S F Hu
Transcriptional activation is important for the elevated expression of human thymidine kinase (hTK) in tumor cells. Here, we used TK(-133/+33)-luciferase reporter gene construct and bandshift assay to study the cis-elements involved in transcriptional activation of the hTK promoter. We found that two CCAAT boxes at -71/-67 and -40/-36 and Sp1 binding site located at -118/-113 were critical for maximal expression of the hTK promoter activity. As Sp1-mediated activation of the hTK promoter was not detectable for the promoter construct with double mutations at two CCAAT boxes, we proposed that NF-Y binding to the hTK promoter sequence is a requisite step for the functional interaction with Sp1...
November 1, 1999: Journal of Cellular Biochemistry
Y H Lee, J S Park, C H Park, S K Lee
Cyclic AMP and insulin exert a synergistic mitogenic effect on Swiss 3T3 cells. Here, we showed that the activity of cyclin A-dependent kinase was elevated 3-fold at 24 h after cotreatment of cells with dibutyryl cAMP and insulin. The cotreatment elevated cyclin A protein levels 12-fold higher than those of insulin-treated cells without altering the levels of CDK2 and p27Kip1 proteins. Interestingly, the half-life of cyclin A protein increased from 7 h in the insulin-treated cells to 22 h in the cotreated cells...
March 27, 1998: Biochemical and Biophysical Research Communications
K S Katula, K L Wright, H Paul, D R Surman, F J Nuckolls, J W Smith, J P Ting, J Yates, J P Cogswell
Control of cell proliferation is dependent on the regulated expression of the cyclin genes. Induction of cyclin B1 gene expression in S phase has been shown to require sequences within the first 90 bp of the proximal promoter region. In this study, we defined the cell cycle regulatory elements within this region and explored the mechanism by which the cyclin B1 gene is activated. A CDE-like element that is important in S-phase regulation of other genes was not required for correct cell cycle expression of cyclin B1...
July 1997: Cell Growth & Differentiation: the Molecular Biology Journal of the American Association for Cancer Research
G B Mills, R Schmandt, S Gibson, B Leung, M Hill, C May, Y F Shi, D R Branch, L Radvanyi, K E Truitt
Activation of the multicomponent interleukin-2 receptor (IL-2R) complex leads to a rapid increase in tyrosine phosphorylation of a number of cellular proteins including the IL-2R beta and IL-2R gamma chains of the IL-2R and the RAF-1 serine threonine kinase. In addition, phosphatidylinositol 3-kinase (PI-3K) protein and activity can be immunoprecipitated with anti-phosphotyrosine and anti-IL-2R beta antibodies from IL-2-activated but not resting T lymphocytes. We have demonstrated that the SH2 (SRC homology 2) domains of the 85 kDa subunit of PI-3K are sufficient to mediate binding of the PI-3K complex to tyrosine phosphorylated, but not non-phosphorylated IL-2R beta, suggesting that tyrosine phosphorylation is an integral component of the activation of PI-3K by the IL-2R...
October 1993: Seminars in Immunology
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