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Flowchart: Preparation: P21
 
 
 
 

J Orthop Res. 2006 Jan 6;24(3):428-437 [Epub ahead of print]

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Cyclin D1 and p21 is elevated in the giant cells of giant cell tumors.

Kandel R, Li SQ, Bell R, Wunder J, Ferguson P, Kauzman A, Diehl JA, Werier J.

Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, 600 University Avenue, Suite 600, Toronto, Ontario M5X 1G5 Canada.

Alterations of cell cycle regulatory proteins, especially those that regulate G1 to S transition, have been implicated in the pathogenesis of a wide variety of human tumors. In previous studies we showed that that there is overexpression of cyclin D1 protein predominately in the giant cell component of giant cell tumors of bone. The purpose of this study was to investigate the mechanisms that may be responsible for cyclin D1 accumulation in giant cell tumors. Giant cell tumors have high levels of cyclin D1 mRNA and the giant cell-enriched population of these tumors have significantly more mRNA and protein expression of cyclin D1 than the mononuclear cell population. The giant cells also expressed higher levels of p21 protein and more p21 bound to cyclin D1 than the mononuclear cells. It is possible that p21 may be contributing to the cyclin D1 accumulation that occurs in the giant cells and perhaps even giant cell formation in these tumors. Additional studies are required to confirm the role of p21 in the pathogenesis of these tumors. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:428-437, 2006.

PMID: 16479604 [PubMed - as supplied by publisher]

     Direct Interaction of p21 with p50, the Small Subunit of Human DNA Polymerase Delta.

Li H, Xie B, Rahmeh A, Zhou Y, Lee MY.

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA.

Using a yeast two-hybrid screening technique and the p50 subunit of human DNA polymerase delta (pol delta) as a bait, p21 was found to interact with the p50 subunit of pol delta. A direct interaction between p21 and p50 was confirmed by using ELISA and pull-down assays with purified proteins. The interaction sites between p50 and p21 were mapped by pull down assays with GST deletion mutants. Residues 127-193 constitute the primary interaction region on p50 to which p21 binds, while p50 binds to the C-terminal 26 residues of p21. A histone kinase activity was associated with the highly purified calf thymus pol delta and addition of purified recombinant p21 inhibited the kinase activity in a dose dependent manner. p50 is phosphorylated in vivo and can be phosphorylated by CDK2/cyclinA in vitro. In vivo evidence of p21 association with p50 was obtained by coimmunoprecipitation using MCF7 cells. It was also shown that the association of p21 with p50 and other components of the pol delta complex increased in MCF7 cells treated with adriamycin. Our results suggested that p50 might target or anchor p21 to pol delta complex upon certain DNA damage such as adriamycin treatment.

PMID: 16479163 [PubMed - as supplied by publisher

Mutat Res. 1999 Dec 16;431(1):123-31.Click here to read Links

Cytogenetic damage and ras p21 oncoprotein levels from patients with chronic obstructive pulmonary disease (COPD), untreated lung cancer and healthy controls.

Cebulska-Wasilewska A, Wierzewska A, Nizankowska E, Graca B, Hughes JA, Anderson D.

Environmental and Radiation Biology Department, Institute of Nuclear Physics, Cracow, Poland. wasilewska@vsb01.ifj.edu.pl

The purpose of the present communication was to determine in patients with chronic obstructive pulmonary disease (COPD), untreated lung cancer and healthy controls if there was a possible association between the disease state and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors such as smoking habit and endogenous ones (sex, cancer in the immediate family) could affect these biomarkers. The individuals in all groups were as well-matched as possible for age to determine if this could be eliminated as a confounder. Peripheral blood and plasma were collected from 20 COPD patients, 31 cancer patients and 20 healthy controls. Chromosomal aberrations (CA), sister chromatid exchanges (SCE) and high frequency SCE cells (HFC) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to the confounding factors. Results were analysed by a t-test, analysis of variance (ANOVA) and stepwise multivariate regression analysis. There was an increase in CA, although not statistically so, in COPD and cancer patients by comparison with healthy controls, but there was a statistically significant increase in SCE, HFC and ras p21 oncoproteins. There was also a statistically significant difference between respiratory volume parameters in COPD patients and controls. Respiratory parameters were not measured in cancer patients. Ras p21 oncoproteins were also statistically significantly increased in the COPD and cancer patients, suggesting that the disease state alone might be sufficient to increase the oncoproteins, or that some of the COPD patients were in the process of developing cancer or perhaps some would die from COPD before cancer developed. Smoking was shown to have a marked effect on all parameters investigated. Ex-smokers showed less effects. Since age was very well controlled, there was little effect due to age. There was an effect due to sex, but cancer in the immediate family had little effect on any of the parameters.

PMID: 10656491 [PubMed - indexed for MEDLINE]

 

 

 

 

 

 

 
                                                                        

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