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. 2000 Nov 22;83(11):1468–1472. doi: 10.1054/bjoc.2000.1464

Expression of the novel tumour suppressor p33ING1 is independent of p53

K-J J Cheung Jr 1, J A Bush 1, W Jia 2, G Li 1
PMCID: PMC2363422  PMID: 11076655

Abstract

A recently cloned tumour suppressor candidate, p33ING1, has been shown in vitro to collaborate with p53 to execute growth arrest and apoptosis. However, it is unclear as to how the expression of ING1 is regulated in normal and stress conditions. Using a p53-knockout mouse model, we investigated if the expression of ING1 was dependent on p53. We found that there was no difference in ING1 mRNA and protein levels between p53+/+ and p53–/– murine organs. In addition, when normal human epithelial keratinocytes (NHEK) and a keratinocyte cell line, HaCaT, which lacks wild-type p53 function, were exposed to UVB irradiation, the expression levels of ING1 were elevated in both NHEK and HaCaT cells. It is interesting, however, that UVB irradiation did not induce ING1 expression in dermal fibroblasts isolated from p53+/+ and p53–/– mice. Based on our findings, we therefore conclude that the expression of ING1 is independent of p53 status. UV induction of ING1 in keratinocytes suggests that ING1 may play a role in cellular stress response and skin carcinogenesis. © 2000 Cancer Research Campaign http://www.bjcancer.com

Keywords: p33ING1, p53, in vivo expression, tumour suppressor gene, UV irradiation

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Selected References

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  1. Bond J. A., Wyllie F. S., Wynford-Thomas D. Escape from senescence in human diploid fibroblasts induced directly by mutant p53. Oncogene. 1994 Jul;9(7):1885–1889. [PubMed] [Google Scholar]
  2. Boukamp P., Petrussevska R. T., Breitkreutz D., Hornung J., Markham A., Fusenig N. E. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol. 1988 Mar;106(3):761–771. doi: 10.1083/jcb.106.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bunz F., Dutriaux A., Lengauer C., Waldman T., Zhou S., Brown J. P., Sedivy J. M., Kinzler K. W., Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 1998 Nov 20;282(5393):1497–1501. doi: 10.1126/science.282.5393.1497. [DOI] [PubMed] [Google Scholar]
  4. Donehower L. A., Harvey M., Slagle B. L., McArthur M. J., Montgomery C. A., Jr, Butel J. S., Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992 Mar 19;356(6366):215–221. doi: 10.1038/356215a0. [DOI] [PubMed] [Google Scholar]
  5. Finlay C. A., Hinds P. W., Levine A. J. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. doi: 10.1016/0092-8674(89)90045-7. [DOI] [PubMed] [Google Scholar]
  6. Garkavtsev I., Grigorian I. A., Ossovskaya V. S., Chernov M. V., Chumakov P. M., Gudkov A. V. The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control. Nature. 1998 Jan 15;391(6664):295–298. doi: 10.1038/34675. [DOI] [PubMed] [Google Scholar]
  7. Garkavtsev I., Kazarov A., Gudkov A., Riabowol K. Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation. Nat Genet. 1996 Dec;14(4):415–420. doi: 10.1038/ng1296-415. [DOI] [PubMed] [Google Scholar]
  8. Garkavtsev I., Riabowol K. Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor. Mol Cell Biol. 1997 Apr;17(4):2014–2019. doi: 10.1128/mcb.17.4.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hall P. A., McKee P. H., Menage H. D., Dover R., Lane D. P. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993 Jan;8(1):203–207. [PubMed] [Google Scholar]
  10. Harper J. W., Adami G. R., Wei N., Keyomarsi K., Elledge S. J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. doi: 10.1016/0092-8674(93)90499-g. [DOI] [PubMed] [Google Scholar]
  11. Helbing C. C., Veillette C., Riabowol K., Johnston R. N., Garkavtsev I. A novel candidate tumor suppressor, ING1, is involved in the regulation of apoptosis. Cancer Res. 1997 Apr 1;57(7):1255–1258. [PubMed] [Google Scholar]
  12. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  13. Lehman T. A., Modali R., Boukamp P., Stanek J., Bennett W. P., Welsh J. A., Metcalf R. A., Stampfer M. R., Fusenig N., Rogan E. M. p53 mutations in human immortalized epithelial cell lines. Carcinogenesis. 1993 May;14(5):833–839. doi: 10.1093/carcin/14.5.833. [DOI] [PubMed] [Google Scholar]
  14. Li G., Bush J. A., Ho V. C. p53-dependent apoptosis in melanoma cells after treatment with camptothecin. J Invest Dermatol. 2000 Mar;114(3):514–519. doi: 10.1046/j.1523-1747.2000.00867.x. [DOI] [PubMed] [Google Scholar]
  15. Li G., Ho V. C., Berean K., Tron V. A. Ultraviolet radiation induction of squamous cell carcinomas in p53 transgenic mice. Cancer Res. 1995 May 15;55(10):2070–2074. [PubMed] [Google Scholar]
  16. Li G., Ho V. C., Mitchell D. L., Trotter M. J., Tron V. A. Differentiation-dependent p53 regulation of nucleotide excision repair in keratinocytes. Am J Pathol. 1997 Apr;150(4):1457–1464. [PMC free article] [PubMed] [Google Scholar]
  17. Li G., Ho V. C. p53-dependent DNA repair and apoptosis respond differently to high- and low-dose ultraviolet radiation. Br J Dermatol. 1998 Jul;139(1):3–10. [PubMed] [Google Scholar]
  18. Li G., Mitchell D. L., Ho V. C., Reed J. C., Tron V. A. Decreased DNA repair but normal apoptosis in ultraviolet-irradiated skin of p53-transgenic mice. Am J Pathol. 1996 Apr;148(4):1113–1123. [PMC free article] [PubMed] [Google Scholar]
  19. Li G., Tron V., Ho V. Induction of squamous cell carcinoma in p53-deficient mice after ultraviolet irradiation. J Invest Dermatol. 1998 Jan;110(1):72–75. doi: 10.1046/j.1523-1747.1998.00090.x. [DOI] [PubMed] [Google Scholar]
  20. Miyashita T., Krajewski S., Krajewska M., Wang H. G., Lin H. K., Liebermann D. A., Hoffman B., Reed J. C. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994 Jun;9(6):1799–1805. [PubMed] [Google Scholar]
  21. Miyashita T., Reed J. C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995 Jan 27;80(2):293–299. doi: 10.1016/0092-8674(95)90412-3. [DOI] [PubMed] [Google Scholar]
  22. Ohmori M., Nagai M., Tasaka T., Koeffler H. P., Toyama T., Riabowol K., Takahara J. Decreased expression of p33ING1 mRNA in lymphoid malignancies. Am J Hematol. 1999 Oct;62(2):118–119. doi: 10.1002/(sici)1096-8652(199910)62:2<118::aid-ajh11>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  23. Oki E., Maehara Y., Tokunaga E., Kakeji Y., Sugimachi K. Reduced expression of p33(ING1) and the relationship with p53 expression in human gastric cancer. Cancer Lett. 1999 Dec 1;147(1-2):157–162. doi: 10.1016/s0304-3835(99)00288-8. [DOI] [PubMed] [Google Scholar]
  24. Owen-Schaub L. B., Zhang W., Cusack J. C., Angelo L. S., Santee S. M., Fujiwara T., Roth J. A., Deisseroth A. B., Zhang W. W., Kruzel E. Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol Cell Biol. 1995 Jun;15(6):3032–3040. doi: 10.1128/mcb.15.6.3032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Saito A., Furukawa T., Fukushige S., Koyama S., Hoshi M., Hayashi Y., Horii A. p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1. J Hum Genet. 2000;45(3):177–181. doi: 10.1007/s100380050206. [DOI] [PubMed] [Google Scholar]
  26. Shaulsky G., Goldfinger N., Tosky M. S., Levine A. J., Rotter V. Nuclear localization is essential for the activity of p53 protein. Oncogene. 1991 Nov;6(11):2055–2065. [PubMed] [Google Scholar]
  27. Shinoura N., Muramatsu Y., Nishimura M., Yoshida Y., Saito A., Yokoyama T., Furukawa T., Horii A., Hashimoto M., Asai A. Adenovirus-mediated transfer of p33ING1 with p53 drastically augments apoptosis in gliomas. Cancer Res. 1999 Nov 1;59(21):5521–5528. [PubMed] [Google Scholar]
  28. Smith M. L., Chen I. T., Zhan Q., Bae I., Chen C. Y., Gilmer T. M., Kastan M. B., O'Connor P. M., Fornace A. J., Jr Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science. 1994 Nov 25;266(5189):1376–1380. doi: 10.1126/science.7973727. [DOI] [PubMed] [Google Scholar]
  29. Toyama T., Iwase H., Watson P., Muzik H., Saettler E., Magliocco A., DiFrancesco L., Forsyth P., Garkavtsev I., Kobayashi S. Suppression of ING1 expression in sporadic breast cancer. Oncogene. 1999 Sep 16;18(37):5187–5193. doi: 10.1038/sj.onc.1202905. [DOI] [PubMed] [Google Scholar]
  30. Tron V. A., Trotter M. J., Ishikawa T., Ho V. C., Li G. p53-dependent regulation of nucleotide excision repair in murine epidermis in vivo. J Cutan Med Surg. 1998 Jul;3(1):16–20. doi: 10.1177/120347549800300104. [DOI] [PubMed] [Google Scholar]
  31. Tron V. A., Trotter M. J., Tang L., Krajewska M., Reed J. C., Ho V. C., Li G. p53-regulated apoptosis is differentiation dependent in ultraviolet B-irradiated mouse keratinocytes. Am J Pathol. 1998 Aug;153(2):579–585. doi: 10.1016/S0002-9440(10)65600-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zeremski M., Hill J. E., Kwek S. S., Grigorian I. A., Gurova K. V., Garkavtsev I. V., Diatchenko L., Koonin E. V., Gudkov A. V. Structure and regulation of the mouse ing1 gene. Three alternative transcripts encode two phd finger proteins that have opposite effects on p53 function. J Biol Chem. 1999 Nov 5;274(45):32172–32181. doi: 10.1074/jbc.274.45.32172. [DOI] [PubMed] [Google Scholar]

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