scholarly journals Growth suppression induced by wild-type p53 protein is accompanied by selective down-regulation of proliferating-cell nuclear antigen expression.

1991 ◽  
Vol 88 (5) ◽  
pp. 1958-1962 ◽  
Author(s):  
W. E. Mercer ◽  
M. T. Shields ◽  
D. Lin ◽  
E. Appella ◽  
S. J. Ullrich
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
P53 Protein ◽  
Antigen Expression ◽  
Growth Suppression ◽  
Nuclear Antigen ◽  
Wild Type ◽  
Down Regulation ◽  
Wild Type P53 ◽  
Proliferating Cell

scholarly journals Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter.

1995 ◽  
Vol 15 (12) ◽  
pp. 6785-6793 ◽  
Author(s):  
C V Shivakumar ◽  
D R Brown ◽  
S Deb ◽  
S P Deb
Keyword(s):  
Binding Site ◽  
Proliferating Cell Nuclear Antigen ◽  
P53 Protein ◽  
Cellular Growth ◽  
Nuclear Antigen ◽  
Wild Type ◽  
P53 Response ◽  
Low Levels ◽  
Wild Type P53 ◽  
Proliferating Cell

The wild-type p53 protein is a transcriptional activator implicated in the control of cellular growth-related gene expression. Here, using a number of different cell lines and transient-transfection-transcription assays, we demonstrate that at low levels, wild-type p53 transactivates the human proliferating cell nuclear antigen (PCNA) promoter. When expressed at a similar level, the tumor-derived p53 mutants did not transactivate the PCNA promoter. We identified a p53-binding site on the human PCNA promoter with which p53 interacts sequence specifically. When placed on a heterologous synthetic promoter, the binding site functions as a wild-type p53 response element in either orientation. Deletion of the p53-binding site renders the PCNA promoter p53 nonresponsive, showing that wild-type p53 transactivates the PCNA promoter by binding to the site. At a higher concentration, wild-type p53 inhibits the PCNA promoter but p53 mutants activate. Transactivation by p53 mutants does not require the p53-binding site. These observations suggest that moderate elevation of the cellular wild-type p53 level induces PCNA production to help in DNA repair.

scholarly journals Characterization of the Proliferating Cell Nuclear Antigen of Leishmania donovani Clinical Isolates and Its Association with Antimony Resistance

2014 ◽  
Vol 58 (6) ◽  
pp. 2997-3007 ◽  
Author(s):  
Rati Tandon ◽  
Sharat Chandra ◽  
Rajendra Kumar Baharia ◽  
Sanchita Das ◽  
Pragya Misra ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Proliferating Cell Nuclear Antigen ◽  
Leishmania Donovani ◽  
Clinical Isolates ◽  
Resistant Isolate ◽  
Nuclear Antigen ◽  
Wild Type ◽  
Content Type ◽  
Sensitive Isolate ◽  
Proliferating Cell

ABSTRACTPreviously, through a proteomic analysis, proliferating cell nuclear antigen (PCNA) was found to be overexpressed in the sodium antimony gluconate (SAG)-resistant clinical isolate compared to that in the SAG-sensitive clinical isolate ofLeishmania donovani. The present study was designed to explore the potential role of the PCNA protein in SAG resistance inL. donovani. For this purpose, the protein was cloned, overexpressed, purified, and modeled. Western blot (WB) and real-time PCR (RT-PCR) analyses confirmed that PCNA was overexpressed by ≥3-fold in the log phase, stationary phase, and peanut agglutinin isolated procyclic and metacyclic stages of the promastigote form and by ∼5-fold in the amastigote form of the SAG-resistant isolate compared to that in the SAG-sensitive isolate.L. donovaniPCNA (LdPCNA) was overexpressed as a green fluorescent protein (GFP) fusion protein in a SAG-sensitive clinical isolate ofL. donovani, and modulation of the sensitivities of the transfectants to pentavalent antimonial (SbV) and trivalent antimonial (SbIII) drugs was assessedin vitroagainst promastigotes and intracellular (J774A.1 cell line) amastigotes, respectively. Overexpression of LdPCNA in the SAG-sensitive isolate resulted in an increase in the 50% inhibitory concentrations (IC50) of SbV(from 41.2 ± 0.6 μg/ml to 66.5 ± 3.9 μg/ml) and SbIII(from 24.0 ± 0.3 μg/ml to 43.4 ± 1.8 μg/ml). Moreover, PCNA-overexpressing promastigote transfectants exhibited less DNA fragmentation compared to that of wild-type SAG-sensitive parasites upon SbIIItreatment. In addition, SAG-induced nitric oxide (NO) production was found to be significantly inhibited in the macrophages infected with the transfectants compared with that in wild-type SAG-sensitive parasites. Consequently, we infer that LdPCNA has a significant role in SAG resistance inL. donovaniclinical isolates, which warrants detailed investigations regarding its mechanism.

The Impact of 5-Azacytidine on Placental Weight, Glycoprotein Pattern and Proliferating Cell Nuclear Antigen Expression in Rat Placenta

Placenta ◽  
2007 ◽  
Vol 28 (8-9) ◽  
pp. 803-811 ◽  
Author(s):  
L. Šerman ◽  
M. Vlahović ◽  
M. Šijan ◽  
F. Bulić-Jakuš ◽  
A. Šerman ◽  
...  
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Antigen Expression ◽  
Placental Weight ◽  
Nuclear Antigen ◽  
The Impact ◽  
Proliferating Cell

scholarly journals An evaluation of antioxidant effects on recovery from postischemic acute renal failure.

1994 ◽  
Vol 4 (8) ◽  
pp. 1588-1597
Author(s):  
R A Zager ◽  
S M Fuerstenberg ◽  
P H Baehr ◽  
D Myerson ◽  
B Torok-Storb
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Dna Fragmentation ◽  
Proliferating Cell Nuclear Antigen ◽  
Antigen Expression ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tubular Necrosis ◽  
Proliferating Cell

Xanthine oxidase (XO) activity and hydroxyl radical (.OH) formation are widely proposed mediators of renal reperfusion injury, potentially altering the severity of, and recovery from, postischemic acute renal failure. The goal of this study was to ascertain whether combination XO inhibitor (oxypurinol) and .OH scavenger (Na benzoate) therapy, given at the time of renal ischemia, alters the extent of: (1) tubular necrosis and filtration failure; (2) DNA fragmentation/apoptosis (assessed in situ by terminal deoxynucleotidyl transferase reactivity); (3) early tubular regenerative responses (proliferating cell nuclear antigen expression; (3H)thymidine incorporation); and (4) the rate and/or degree of functional and morphologic repair. The effects of XO inhibition, .OH scavengers, and "catalytic" iron (FeSO4) on human proximal tubular cell proliferation in vitro were also assessed with a newly established cell line (HK-2). Male Sprague-Dawley rats were subjected to 35 min of bilateral renal arterial occlusion with or without oxypurinol/benzoate therapy. These agents did not alter the extent of tubular necrosis or filtration failure, proliferating cell nuclear antigen expression or thymidine incorporation, or the rate/extent of renal functional/morphologic repair. DNA fragmentation did not precede tubular necrosis, and it was unaffected by antioxidant therapy. By 5 days postischemia, both treatment groups demonstrated regenerating epithelial fronds that protruded into the lumina. These structures contained terminal deoxynucleotidyl transferase-reactive, but morphologically intact, cells, suggesting the presence of apoptosis. Oxypurinol and .OH scavengers (benzoate; dimethylthiourea) suppressed in vitro tubular cell proliferation; conversely, catalytic Fe had a growth-stimulatory effect. These results suggest that: (1) XO inhibition/.OH scavenger therapy has no discernible net effect on postischemic acute renal failure; (2) DNA fragmentation does not precede tubular necrosis, suggesting that it is not a primary mediator of ischemic cell death; and (3) antioxidants can be antiproliferative for human tubular cells, possibly mitigating their potential beneficial effects.

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