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Pcna  -  proliferating cell nuclear antigen

Rattus norvegicus

Synonyms: Cyclin, PCNA, PCNAR, Pcna/cyclin, Proliferating cell nuclear antigen
 
 
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Disease relevance of Pcna

 

High impact information on Pcna

  • A calmodulin-dependent process is required for cyclin degradation to occur in cell-free extracts prepared from metaphase II-arrested eggs (CSF extracts) when the free Ca2+ concentration is transiently raised in the physiological micromolar range [6].
  • This consists of at least two subunits, a polypeptide of relative molecular mass 45,000-62,000 (Mr 45-62K) known as cyclin, and a 34K catalytic subunit which has serine/threonine kinase activity and is known as cdc2 kinase [7].
  • The activity of CDK4 is controlled by the opposing effects of the D-type cyclin, an activating subunit, and p16INK4, an inhibitory subunit [8].
  • Cyclic AMP inhibited 63 percent of the cells, while the 8-parachlorophenylthio- and 8-benzylthio- analogs of cyclin AMP inhibited the spontaneous firing of 92 and 89 percent of cells, respectively [9].
  • Cooperating oncogenes converge to regulate cyclin/cdk complexes [10].
 

Chemical compound and disease context of Pcna

  • PCNA labeling index (LI) and the level of PGE2 in bladder papilloma are much higher than those in normal bladder (P<0.01), but lower than those in bladder TCC (P<0.05) [11].
  • The role of G1 cyclin/cdk in Ang II-induced cardiac myocyte hypertrophy by overexpressing cdk inhibitor p21Cip1/Waf1 or p16INK4a was also examined using recombinant adenoviral vectors encoding these genes [12].
  • In animals treated with dimethylhydrazine (DMH), crypt hyperplasia, an increased PCNA labeling index, and shifts in both the region of maximal and the upper extent of PCNA expression were observed during DMH exposure; significant crypt hyperplasia and expansion of the PCNA-positive compartment persisted after completion of DMH injections [13].
  • Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [(3)H]thymidine incorporation (r = -0.61, P <.005), PCNA protein expression (r = -0.62, P <.005), and serum bilirubin (r = -0.49, P <.05) [14].
  • At 11 days postinjection all animals given PA, whether on probucol or not, developed marked proteinuria with histologically minimal glomerular change and significant increases in intraglomerular monocyte and proliferating cell nuclear antigen counts [15].
 

Biological context of Pcna

  • Renal cell apoptosis and proliferation were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and staining with antibody against proliferating cell nuclear antigen (PCNA), respectively [16].
  • PCNA may have contributed to the repair of DNA damage and to cell proliferation caused by exposure to these pollutants [17].
  • Borderzone cardiomyocyte cell cycle activation was demonstrated by increased PCNA (40.1+/-2.6 versus 9.3+/-1.1; P<0.0001), Ki-67 (46.3+/-7.2 versus 20.4+/-6.0; P<0.0001), BrdU (44.2+/-13.7 versus 5.2+/-5.2; P<0.05), and phosphohistone-H3 (12.7+/-1.4 versus 0+/-0; P<0.0001) positive cells/hpf [18].
  • Because of its possible relationship with cell proliferation, PCNA/cyclin has been receiving attention [3].
  • The deduced amino acid sequence and composition of rat PCNA/cyclin are in excellent agreement with the published data [3].
 

Anatomical context of Pcna

 

Associations of Pcna with chemical compounds

  • TUNEL- and PCNA-positive cells were mainly seen in the tubulointerstitial region of Ang II-infused rats [16].
  • Ang II induced increased positivity of TUNEL, and PCNA was blocked completely by losartan, but only partially by hydralazine [16].
  • Besides PCNA, GEN effects on the uterine mRNA expression of IGF-1, IGF-1R, Complement C3, estrogen receptor-alpha (ERalpha) and -beta (ERbeta), as well as progesterone receptor were investigated in intact and OVX co-treated animals [22].
  • Dex treatment induced shrinkage of adrenals where no PCNA-expressing cells were detected, but most of the cells expressed p27Kip1 [20].
  • RESULTS: The basal cells of the GE were actively proliferating, but in the JE, only a few cells were positive for BrdU or PCNA immunostaining [23].
 

Physical interactions of Pcna

  • In conclusion, liver development is associated with a switch from cyclin D2/D3-containing complexes to cyclin D1:CDK4 complexes [24].
  • Our data also present more evidence for a strict functional interdependency between G1 cyclin/CDK complexes and c-Myc [25].
  • Western assays demonstrated, further, that cyclin D3 was complexed with the cyclin dependent-kinases, cdk2 and cdk4, in differentiated L6 cells [26].
  • Application of markers for cell proliferation activities including proliferating cell nuclear antigen (PCNA) and silver-binding nucleolar organizer regions (AgNORs) also revealed significantly elevated AgNOR counts in the long-term group TCC [27].
 

Regulatory relationships of Pcna

  • In fibroblasts, activation of MAPK induces the expression of type D cyclin, whereas, in MCs, this induction has not been shown [28].
  • These data show first that Myc controls the activity of G1 cyclin-dependent kinases independently from the transition between quiescence and proliferation and from any effect on cell growth in size [29].
  • In androgen-replete rats, proliferating cell nuclear antigen-positive cells co-expressed AR (12.7%), P-ERK (36.4%), and P-ERK + AR (45.0%); 5.9% were probably stimulated by other mitogenic mechanisms [30].
  • The results demonstrate that cyclin D1 induction is one of the earlier events in hepatocyte proliferation induced by T3 and suggest that this cyclin might be a common target responsible for the mitogenic activity of ligands of nuclear receptors [31].
  • Both S phase entry and activation of cyclin/CDKs were inhibited by over expression of p27 [32].
 

Other interactions of Pcna

  • In experiment 2, numbers (0.65 +/- 0.57 vs 0.17 +/- 0.28 in the 0%) and areas (0.005 +/- 0.005 vs 0.0007 +/- 0.0012 in the 0%) of GST-P-positive foci and hepatocellular proliferating cell nuclear antigen (PCNA) expression (3.8 +/- 2.3 vs 2.6 +/- 0.7 in the 0%) were significantly increased by the 2% treatment [19].
  • The following variables were studied: volume fraction (VF) of Bcl-2 immunostaining, percentage of cells immunoreactive to proliferating cell nuclear antigen (LIPCNA) and p53 (LIp53), numerical density of caspase-3 immunoreactive cells (NV caspase-3), and estimates of volume-weighted mean nuclear volume (upsilonV) [33].
  • By contrast, significantly stronger beta-catenin and Cyclin D1 mRNA expressions and protein levels were found in CsA-treated rats than controls by RT-PCR and immunohistochemistry at week 4, whereas PCNA production was stronger at both times [34].
  • Correlation analyses showed that IMDI had a negative correlation with ITF mRNA and PCNA (r = -0.543, P<0.05; r = -0.794, P<0.01, respectively) [2].
  • Samples were also subjected to immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) and caspase 3 [23].
 

Analytical, diagnostic and therapeutic context of Pcna

References

  1. Carbon monoxide promotes hypoxic pulmonary vascular remodeling. Carraway, M.S., Ghio, A.J., Suliman, H.B., Carter, J.D., Whorton, A.R., Piantadosi, C.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  2. Expression of intestinal trefoil factor, proliferating cell nuclear antigen and histological changes in intestine of rats after intrauterine asphyxia. Xu, L.F., Li, J., Sun, M., Sun, H.W. World J. Gastroenterol. (2005) [Pubmed]
  3. Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin. Matsumoto, K., Moriuchi, T., Koji, T., Nakane, P.K. EMBO J. (1987) [Pubmed]
  4. DNA synthesis enzymes and proliferating cell nuclear antigen in normal and neoplastic nerve cells. Verri, A., Verzeletti, S., Mazzarello, P., Spadari, S., Negri, M., Bunone, G., Della Valle, G., Hübscher, U., Focher, F. Anticancer Res. (1992) [Pubmed]
  5. Induction of glutathione S-transferase placental form positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks. Shen, J., Wanibuchi, H., Salim, E.I., Wei, M., Doi, K., Yoshida, K., Endo, G., Morimura, K., Fukushima, S. Toxicol. Appl. Pharmacol. (2003) [Pubmed]
  6. Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Lorca, T., Cruzalegui, F.H., Fesquet, D., Cavadore, J.C., Méry, J., Means, A., Dorée, M. Nature (1993) [Pubmed]
  7. Phosphorylation of non-muscle caldesmon by p34cdc2 kinase during mitosis. Yamashiro, S., Yamakita, Y., Hosoya, H., Matsumura, F. Nature (1991) [Pubmed]
  8. Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Serrano, M., Gómez-Lahoz, E., DePinho, R.A., Beach, D., Bar-Sagi, D. Science (1995) [Pubmed]
  9. Analogs of cyclic adenosine monophosphate: correlation of inhibition of Purkinje Neurons with Protein Kinase Activation. Siggins, G.R., Henriksen, S.J. Science (1975) [Pubmed]
  10. Cooperating oncogenes converge to regulate cyclin/cdk complexes. Lloyd, A.C., Obermüller, F., Staddon, S., Barth, C.F., McMahon, M., Land, H. Genes Dev. (1997) [Pubmed]
  11. Elevated prostaglandin E2 level via cPLA2--COX-2--mPGES-1 pathway involved in bladder carcinogenesis induced by terephthalic acid-calculi in Wistar rats. Shi, Y., Cui, L., Dai, G., Chen, J., Pan, H., Song, L., Cheng, S., Wang, X. Prostaglandins Leukot. Essent. Fatty Acids (2006) [Pubmed]
  12. G1 cyclins are involved in the mechanism of cardiac myocyte hypertrophy induced by angiotensin II. Nozato, T., Ito, H., Tamamori, M., Adachi, S., Abe, S., Marumo, F., Hiroe, M. Jpn. Circ. J. (2000) [Pubmed]
  13. Proliferating cell nuclear antigen expression in normal, preneoplastic, and neoplastic colonic epithelium of the rat. Yamada, K., Yoshitake, K., Sato, M., Ahnen, D.J. Gastroenterology (1992) [Pubmed]
  14. Regenerative activity and liver function following partial hepatectomy in the rat using (31)P-MR spectroscopy. Corbin, I.R., Buist, R., Volotovskyy, V., Peeling, J., Zhang, M., Minuk, G.Y. Hepatology (2002) [Pubmed]
  15. Inhibition of progression of chronic puromycin aminonucleoside nephrosis by probucol, an antioxidant. Magil, A. J. Am. Soc. Nephrol. (1996) [Pubmed]
  16. Different effects of angiotensin II and catecholamine on renal cell apoptosis and proliferation in rats. Aizawa, T., Ishizaka, N., Kurokawa, K., Nagai, R., Nakajima, H., Taguchi, J., Ohno, M. Kidney Int. (2001) [Pubmed]
  17. cDNA microarray analysis of gene expression in rat alveolar macrophages in response to organic extract of diesel exhaust particles. Koike, E., Hirano, S., Shimojo, N., Kobayashi, T. Toxicol. Sci. (2002) [Pubmed]
  18. Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure. Woo, Y.J., Panlilio, C.M., Cheng, R.K., Liao, G.P., Atluri, P., Hsu, V.M., Cohen, J.E., Chaudhry, H.W. Circulation (2006) [Pubmed]
  19. Enhancement of hepatocarcinogenesis by kojic acid in rat two-stage models after initiation with N-bis(2-hydroxypropyl)nitrosamine or N-diethylnitrosamine. Takizawa, T., Imai, T., Onose, J., Ueda, M., Tamura, T., Mitsumori, K., Izumi, K., Hirose, M. Toxicol. Sci. (2004) [Pubmed]
  20. Differential expression of cyclin-dependent kinase inhibitors, p27Kip1 and p57Kip2, by corticotropin in rat adrenal cortex. Kobayashi, H., Kambe, F., Imai, T., Hibi, Y., Kikumori, T., Ohmori, S., Nakao, A., Seo, H. J. Endocrinol. (2006) [Pubmed]
  21. Effects of interleukin-11 and epidermal growth factor on residual small intestine after experimental massive small bowel resection. Ledniczky, G., Fiore, N., Bognár, G., Ondrejka, P., Grosfeld, J.L. Chirurgia (Bucharest, Romania : 1990) (2006) [Pubmed]
  22. Combinatorial effects of the phytoestrogen genistein and of estradiol in uterus and liver of female Wistar rats. Diel, P., Hertrampf, T., Seibel, J., Laudenbach-Leschowsky, U., Kolba, S., Vollmer, G. J. Steroid Biochem. Mol. Biol. (2006) [Pubmed]
  23. Junctional epithelium in rats is characterized by slow cell proliferation. Willberg, J., Syrjänen, S., Hormia, M. J. Periodontol. (2006) [Pubmed]
  24. D-type cyclins and G1 progression during liver development in the rat. Boylan, J.M., Gruppuso, P.A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  25. Malignant transformation by cyclin E and Ha-Ras correlates with lower sensitivity towards induction of cell death but requires functional Myc and CDK4. Haas, K., Johannes, C., Geisen, C., Schmidt, T., Karsunky, H., Blass-Kampmann, S., Obe, G., Möröy, T. Oncogene (1997) [Pubmed]
  26. Expression of the positive regulator of cell cycle progression, cyclin D3, is induced during differentiation of myoblasts into quiescent myotubes. Kiess, M., Gill, R.M., Hamel, P.A. Oncogene (1995) [Pubmed]
  27. Progressive growth of rat bladder carcinomas after exposure to prolonged uracil-induced urolithiasis. Shibata, M.A., Shirai, T., Takahashi, S., Takesada, Y., Iwata, H., Okumura, M., Fukushima, S. Teratog., Carcinog. Mutagen. (1994) [Pubmed]
  28. Role of cyclins in cAMP inhibition of glomerular mesangial cell proliferation. Ito, C., Yamamoto, H., Furukawa, Y., Takeda, S., Akimoto, T., Iimura, O., Ando, Y., Asano, Y., Kusano, E. Clin. Sci. (2004) [Pubmed]
  29. Activation of c-Myc uncouples DNA replication from activation of G1-cyclin-dependent kinases. Pusch, O., Bernaschek, G., Eilers, M., Hengstschläger, M. Oncogene (1997) [Pubmed]
  30. Androgen receptor pathway in rats with autosomal dominant polycystic kidney disease. Nagao, S., Kusaka, M., Nishii, K., Marunouchi, T., Kurahashi, H., Takahashi, H., Grantham, J. J. Am. Soc. Nephrol. (2005) [Pubmed]
  31. Cyclin D1 is an early target in hepatocyte proliferation induced by thyroid hormone (T3). Pibiri, M., Ledda-Columbano, G.M., Cossu, C., Simbula, G., Menegazzi, M., Shinozuka, H., Columbano, A. FASEB J. (2001) [Pubmed]
  32. The mechanism of cell cycle regulation by v-Src. Riley, D., Carragher, N.O., Frame, M.C., Wyke, J.A. Oncogene (2001) [Pubmed]
  33. Immunohistochemical study of cell proliferation, Bcl-2, p53, and caspase-3 expression on preneoplastic changes induced by cadmium and zinc chloride in the ventral rat prostate. Arriazu, R., Pozuelo, J.M., Henriques-Gil, N., Perucho, T., Martín, R., Rodríguez, R., Santamaría, L. J. Histochem. Cytochem. (2006) [Pubmed]
  34. Cyclosporin-induced downregulation of the expression of E-cadherin during proliferation of edentulous gingival epithelium in rats. Tu, H.P., Chen, Y.T., Shieh, Y.S., Chin, Y.T., Huang, R.Y., Yang, S.F., Gau, C.H., Fu, E. J. Periodontol. (2006) [Pubmed]
  35. Epidermal growth factor receptor-mediated proliferation of enterocytes requires p21waf1/cip1 expression. Sheng, G., Bernabe, K.Q., Guo, J., Warner, B.W. Gastroenterology (2006) [Pubmed]
  36. Bound PCNA in nuclei of primary rat tracheal epithelial cells after exposure to very low doses of plutonium-238 alpha particles. Hill, M.A., Ford, J.R., Clapham, P., Marsden, S.J., Stevens, D.L., Townsend, K.M., Goodhead, D.T. Radiat. Res. (2005) [Pubmed]
 
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