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Gene Review

Pcna  -  proliferating cell nuclear antigen

Mus musculus

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


Psychiatry related information on Pcna


High impact information on Pcna


Chemical compound and disease context of Pcna


Biological context of Pcna

  • Together with evidence accumulated in vitro, these results strongly support the idea that the Pcna-dependent pathway predominantly acts in BER of radiation-induced DNA damage in vivo [18].
  • The structural gene for proliferating cell nuclear antigen (Pcna) has been mapped to mouse Chromosome (Chr) 2 by use of a PCR-based assay [19].
  • The determined gene order is we-0.09 +/- 0.09-Itp-0.62 +/- 0.23-D2Mit77-0.26 +/- 0.15-[Evi-4, Pcna, Prn-p]-0.26 +/- 0.15-Scg-1-0.44 +/- 0.19-[Bmp2a, D2Mit70]-0.09 +/-. 0.09-[D2Mit19, D2Mit46]-1.59 +/- 0.36-D2Mit28-0.97 +/- 0.28-D2Ler1-1.50 +/- 0.35-H-3b-0.26 +/- 0.15-un (% recombination +/- 1 SE) [20].
  • The orderly progression through the cell cycle is mediated by the sequential activation of several cyclin/cyclin-dependent kinase (cdk) complexes [21].
  • Here we show that in noncycling developing thymocytes, the cyclin- dependent kinase Cdk2 is activated in response to all specific and nonspecific apoptotic stimuli tested, including peptide-specific thymocyte apoptosis [22].

Anatomical context of Pcna


Associations of Pcna with chemical compounds


Physical interactions of Pcna


Enzymatic interactions of Pcna


Regulatory relationships of Pcna

  • Our data provide evidence that p21 regulates the PCNA protein level in adult cardiomyocytes, which has implications for cardiomyocyte growth control [34].
  • These results demonstrate that TGF-beta stimulates cyclin D(1) expression at least in part through activation of beta-catenin signaling [35].
  • Unlike the earlier expression of Ras(Asn17) at the border between G0 and G1, its delayed expression did not compromise the EGF-stimulated transient activation of extracellular signal-regulated kinases or inhibit the stimulated expression of a principal D-type cyclin, cyclin D1, until close to the border between G1 and S [36].
  • Thus, the redundant pathways consisting of cyclin proteolysis and CKIs control CDK activity during mitotic exit and contribute to maintenance of genome stability in mammalian cells [37].
  • Tyr-Phe and Met limitation in vitro inhibited cell proliferation and proliferating cell nuclear antigen (PCNA) expression to a greater extent than serum limitation [38].

Other interactions of Pcna


Analytical, diagnostic and therapeutic context of Pcna


  1. Elevated levels of cyclin D1 protein in response to increased expression of eukaryotic initiation factor 4E. Rosenwald, I.B., Lazaris-Karatzas, A., Sonenberg, N., Schmidt, E.V. Mol. Cell. Biol. (1993) [Pubmed]
  2. Expression of E1A in terminally differentiated muscle cells reactivates the cell cycle and suppresses tissue-specific genes by separable mechanisms. Tiainen, M., Spitkovsky, D., Jansen-Dürr, P., Sacchi, A., Crescenzi, M. Mol. Cell. Biol. (1996) [Pubmed]
  3. Disruption of the FEN-1/PCNA Interaction Results in DNA Replication Defects, Pulmonary Hypoplasia, Pancytopenia, and Newborn Lethality in Mice. Zheng, L., Dai, H., Qiu, J., Huang, Q., Shen, B. Mol. Cell. Biol. (2007) [Pubmed]
  4. Early increase in cyclin-D1 expression and accelerated entry of mouse hepatocytes into S phase after administration of the mitogen 1, 4-Bis[2-(3,5-Dichloropyridyloxy)] benzene. Ledda-Columbano, G.M., Pibiri, M., Loi, R., Perra, A., Shinozuka, H., Columbano, A. Am. J. Pathol. (2000) [Pubmed]
  5. The cyclin kinase inhibitor p21WAF1/CIP1 is required for glomerular hypertrophy in experimental diabetic nephropathy. Al-Douahji, M., Brugarolas, J., Brown, P.A., Stehman-Breen, C.O., Alpers, C.E., Shankland, S.J. Kidney Int. (1999) [Pubmed]
  6. Cyclin A activates the DNA polymerase delta -dependent elongation machinery in vitro: A parvovirus DNA replication model. Bashir, T., Horlein, R., Rommelaere, J., Willwand, K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. Proliferating cell nuclear antigen immunohistochemistry in astrocytes in experimental Creutzfeldt-Jakob disease and in human kuru, Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker syndrome. Biernat, W., Liberski, P.P., Guiroy, D.C., Yanagihara, R., Gajdusek, D.C. Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration. (1995) [Pubmed]
  8. Mouse development and cell proliferation in the absence of D-cyclins. Kozar, K., Ciemerych, M.A., Rebel, V.I., Shigematsu, H., Zagozdzon, A., Sicinska, E., Geng, Y., Yu, Q., Bhattacharya, S., Bronson, R.T., Akashi, K., Sicinski, P. Cell (2004) [Pubmed]
  9. Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6. Malumbres, M., Sotillo, R., Santamaría, D., Galán, J., Cerezo, A., Ortega, S., Dubus, P., Barbacid, M. Cell (2004) [Pubmed]
  10. Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins. Swanton, C., Mann, D.J., Fleckenstein, B., Neipel, F., Peters, G., Jones, N. Nature (1997) [Pubmed]
  11. Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1. Luo, Y., Hurwitz, J., Massagué, J. Nature (1995) [Pubmed]
  12. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Holmgren, L., O'Reilly, M.S., Folkman, J. Nat. Med. (1995) [Pubmed]
  13. The cyclin kinase inhibitor p21CIP1/WAF1 limits glomerular epithelial cell proliferation in experimental glomerulonephritis. Kim, Y.G., Alpers, C.E., Brugarolas, J., Johnson, R.J., Couser, W.G., Shankland, S.J. Kidney Int. (1999) [Pubmed]
  14. The herbal medicine sho-saiko-to inhibits the growth of malignant melanoma cells by upregulating Fas-mediated apoptosis and arresting cell cycle through downregulation of cyclin dependent kinases. Liu, W., Kato, M., Akhand, A.A., Hayakawa, A., Takemura, M., Yoshida, S., Suzuki, H., Nakashima, I. Int. J. Oncol. (1998) [Pubmed]
  15. Greater expression of transforming growth factor alpha and proliferating cell nuclear antigen staining in mouse hepatoblastomas than hepatocellular carcinomas induced by a diethylnitrosamine-sodium phenobarbital regimen. Sakairi, T., Kobayashi, K., Goto, K., Okada, M., Kusakabe, M., Tsuchiya, T., Sugimoto, J., Sano, F., Mutai, M. Toxicologic pathology. (2001) [Pubmed]
  16. Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine. Kakizaki, S., Takagi, H., Fukusato, T., Toyoda, M., Horiguchi, N., Sato, K., Takayama, H., Nagamine, T., Mori, M. International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition. (2001) [Pubmed]
  17. High glucose-induced hypertrophy of mesangial cells requires p27(Kip1), an inhibitor of cyclin-dependent kinases. Wolf, G., Schroeder, R., Zahner, G., Stahl, R.A., Shankland, S.J. Am. J. Pathol. (2001) [Pubmed]
  18. Biological response to ionizing radiation in mouse embryo fibroblasts with a targeted disruption of the DNA polymerase beta gene. Miura, M., Watanabe, H., Okochi, K., Sasaki, T., Shibuya, H. Radiat. Res. (2000) [Pubmed]
  19. The gene for proliferating cell nuclear antigen (Pcna) maps to mouse chromosome 2. Abbott, C., Pilz, A., Moseley, H., Peter, J. Mamm. Genome (1992) [Pubmed]
  20. High-resolution mapping of a minor histocompatibility antigen gene on mouse chromosome 2. Zuberi, A.R., Roopenian, D.C. Mamm. Genome (1993) [Pubmed]
  21. Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes. Beijersbergen, R.L., Carlée, L., Kerkhoven, R.M., Bernards, R. Genes Dev. (1995) [Pubmed]
  22. The cyclin-dependent kinase Cdk2 regulates thymocyte apoptosis. Hakem, A., Sasaki, T., Kozieradzki, I., Penninger, J.M. J. Exp. Med. (1999) [Pubmed]
  23. Deficiency of the cyclin kinase inhibitor p21(WAF-1/CIP-1) promotes apoptosis of activated/memory T cells and inhibits spontaneous systemic autoimmunity. Lawson, B.R., Baccala, R., Song, J., Croft, M., Kono, D.H., Theofilopoulos, A.N. J. Exp. Med. (2004) [Pubmed]
  24. Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice. Soonpaa, M.H., Koh, G.Y., Pajak, L., Jing, S., Wang, H., Franklin, M.T., Kim, K.K., Field, L.J. J. Clin. Invest. (1997) [Pubmed]
  25. Activation of mouse natural killer T cells accelerates liver regeneration after partial hepatectomy. Nakashima, H., Inui, T., Habu, Y., Kinoshita, M., Nagao, S., Kawaguchi, A., Miura, S., Shinomiya, N., Yagita, H., Seki, S. Gastroenterology (2006) [Pubmed]
  26. p18(INK4c) collaborates with other CDK-inhibitory proteins in the regenerating liver. Luedde, T., Rodriguez, M.E., Tacke, F., Xiong, Y., Brenner, D.A., Trautwein, C. Hepatology (2003) [Pubmed]
  27. Inhibition of mitogenesis in Balb/c-3T3 cells by Trichostatin A. Multiple alterations in the induction and activation of cyclin-cyclin-dependent kinase complexes. Wharton, W., Savell, J., Cress, W.D., Seto, E., Pledger, W.J. J. Biol. Chem. (2000) [Pubmed]
  28. Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin. Reagan-Shaw, S., Afaq, F., Aziz, M.H., Ahmad, N. Oncogene (2004) [Pubmed]
  29. Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage. Kallay, E., Pietschmann, P., Toyokuni, S., Bajna, E., Hahn, P., Mazzucco, K., Bieglmayer, C., Kato, S., Cross, H.S. Carcinogenesis (2001) [Pubmed]
  30. Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo. Zschemisch, N.H., Liedtke, C., Dierssen, U., Nevzorova, Y.A., Wüstefeld, T., Borlak, J., Manns, M.P., Trautwein, C. Hepatology (2006) [Pubmed]
  31. Activation of cyclin-dependent kinases by Myc mediates induction of cyclin A, but not apoptosis. Rudolph, B., Saffrich, R., Zwicker, J., Henglein, B., Müller, R., Ansorge, W., Eilers, M. EMBO J. (1996) [Pubmed]
  32. Site-directed mutant p21 proteins defective in both inhibition of E2F-regulated transcription and disruption of E2F-p130-cyclin-cdk2 complexes. Robles, S.J., Shiyanov, P., Aristodemo, G.T., Raychaudhuri, P., Adami, G.R. DNA Cell Biol. (1998) [Pubmed]
  33. Functional analysis of cyclin D2 and p27(Kip1) in cyclin D2 transgenic mouse mammary gland during development. Kong, G., Chua, S.S., Yijun, Y., Kittrell, F., Moraes, R.C., Medina, D., Said, T.K. Oncogene (2002) [Pubmed]
  34. p21(CIP1) Controls proliferating cell nuclear antigen level in adult cardiomyocytes. Engel, F.B., Hauck, L., Boehm, M., Nabel, E.G., Dietz, R., von Harsdorf, R. Mol. Cell. Biol. (2003) [Pubmed]
  35. Transforming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes. Li, T.F., Chen, D., Wu, Q., Chen, M., Sheu, T.J., Schwarz, E.M., Drissi, H., Zuscik, M., O'Keefe, R.J. J. Biol. Chem. (2006) [Pubmed]
  36. Ras activity late in G1 phase required for p27kip1 downregulation, passage through the restriction point, and entry into S phase in growth factor-stimulated NIH 3T3 fibroblasts. Takuwa, N., Takuwa, Y. Mol. Cell. Biol. (1997) [Pubmed]
  37. Cyclin proteolysis and CDK inhibitors: two redundant pathways to maintain genome stability in mammalian cells. Chibazakura, T. Cell Cycle (2004) [Pubmed]
  38. Tyrosine and phenylalanine restriction induces G0/G1 cell cycle arrest in murine melanoma in vitro and in vivo. Fu, Y.M., Yu, Z.X., Ferrans, V.J., Meadows, G.G. Nutrition and cancer. (1997) [Pubmed]
  39. Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). Hiromura, K., Pippin, J.W., Fero, M.L., Roberts, J.M., Shankland, S.J. J. Clin. Invest. (1999) [Pubmed]
  40. Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas. Vinter-Jensen, L., Juhl, C.O., Teglbjaerg, P.S., Poulsen, S.S., Dajani, E.Z., Nexø, E. Gastroenterology (1997) [Pubmed]
  41. Strain-dependent embryonic lethality in mice lacking the retinoblastoma-related p130 gene. LeCouter, J.E., Kablar, B., Whyte, P.F., Ying, C., Rudnicki, M.A. Development (1998) [Pubmed]
  42. Cyclin A2-CDK2 regulates embryonic gene activation in 1-cell mouse embryos. Hara, K.T., Oda, S., Naito, K., Nagata, M., Schultz, R.M., Aoki, F. Dev. Biol. (2005) [Pubmed]
  43. Smooth muscle differentiation and cell turnover in mouse detrusor development. Smeulders, N., Woolf, A.S., Wilcox, D.T. J. Urol. (2002) [Pubmed]
  44. Apoptosis and proliferation of endothelial cells in early atherosclerotic lesions: possible role of oxidised LDL. Norata, G.D., Tonti, L., Roma, P., Catapano, A.L. Nutrition, metabolism, and cardiovascular diseases : NMCD. (2002) [Pubmed]
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