This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goeman, F. Articles by Baniahmad, A. Search for Related Content PubMed PubMed Citation Articles by Goeman, F. Articles by Baniahmad, A.

Growth Inhibition by the Tumor Suppressor p33ING1 in Immortalized and Primary Cells: Involvement of Two Silencing Domains and Effect of Ras

Frauke Goeman,^1, Dorit Thormeyer,^1,, Maria Abad,² Manuel Serrano,³ Oliver Schmidt,¹ Ignacio Palmero,² and Aria Baniahmad^1*

Genetic Institute, Justus Liebig University, Giessen, Germany,¹ Instituto de Investigaciones Biomédicas,² Centro Nacional de Investigaciones Oncológicas, CNIO, Madrid, Spain³

Received 5 May 2004/ Returned for modification 2 June 2004/ Accepted 16 September 2004

ING1 was identified as an inhibitor of growth and has been described as a tumor suppressor. Furthermore, the expression of ING1 is induced in senescent cells and antisense ING1 extends the proliferative life span of primary human fibroblasts. Cooperation of p33ING1 with p53 has been suggested to be an important function of ING1 in cell cycle control. Intriguingly, it has been shown that p33ING1 is associated with histone acetylation as well as with histone deacetylation function. Here we show that p33ING1 is a potent transcriptional silencer in various cell types. However, the silencing function is independent of the presence of p53. By use of deletion mutants two potent autonomous and transferable silencing domains were identified, but no evidence of an activation domain was found. The amino (N)-terminal silencing domain is sensitive to the histone deacetylase inhibitor trichostatin A (TSA) whereas the carboxy-terminal silencing function is resistant to TSA, suggesting that p33ING1 confers gene silencing through both HDAC-dependent and -independent mechanisms. Interestingly, the presence of oncogenic Ras, which is able to induce premature senescence, increases the p33ING1-mediated silencing function. Moreover, ING1-mediated silencing was reduced by coexpressing dominant-negative Ras or by treatment with the mitogen-activated protein kinase inhibitor PD98059 but not by treatment with SB203580, an inhibitor of the p38 pathway. In addition, we show that both silencing domains of ING1 are involved in cell cycle control, as measured by inhibition of colony formation of immortalized cells and by thymidine incorporation of primary human diploid fibroblasts (HDF). Interestingly, p33ING1 expression induces features of cellular senescence in HDFs.

F.G. and D.T. contributed equally.

Present address: Fachklinik Hornheide, University Münster, 48157 Münster, Germany.

This article has been cited by other articles:

• Abad, M., Menendez, C., Fuchtbauer, A., Serrano, M., Fuchtbauer, E.-M., Palmero, I. (2007). Ing1 Mediates p53 Accumulation and Chromatin Modification in Response to Oncogenic Stress. J. Biol. Chem. 282: 31060-31067 [Abstract] [Full Text]  
• Coles, A. H., Liang, H., Zhu, Z., Marfella, C. G.A., Kang, J., Imbalzano, A. N., Jones, S. N. (2007). Deletion of p37Ing1 in Mice Reveals a p53-Independent Role for Ing1 in the Suppression of Cell Proliferation, Apoptosis, and Tumorigenesis. Cancer Res. 67: 2054-2061 [Abstract] [Full Text]