Abstract
The transcription regulation activity of p53 controls cellular response to a variety of stress conditions, leading to growth arrest and apoptosis. Despite major progress in the understanding of the global effects of p53 on cellular function the pathways by which p53 activates apoptosis are not well defined. To study genes activated in the p53 induced apoptotic process, we used a mouse myeloid leukemic cell line (LTR6) expressing the temperature-sensitive p53 (val135) that undergoes apoptosis upon shifting the temperature to 32°C. We analysed the gene expression profile at different time points after p53 activation using oligonucleotide microarray capable of detecting ∼11 000 mRNA species. Cluster analysis of the p53-regulated genes indicate a pattern of early and late induced sets of genes. We show that 91 and 44 genes were substantially up and down regulated, respectively, by p53. Functional classification of these genes reveals that they are involved in many aspects of cell function, in addition to growth arrest and apoptosis. Comparison of p53 regulated gene expression profile in LTR6 cells to that of a human lung cancer cell line (H1299) that undergoes growth arrest but not apoptosis demonstrates that only 15% of the genes are common to both systems. This observation supports the presence of two distinct transcriptional programs in response to p53 signaling, one leading to growth arrest and the other to apoptosis. The proapoptotic genes induced only in LTR6 cells like Apaf-1, Sumo-1 and gelsolin among others may suggest a possible explanation for apoptosis in LTR6 cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cecconi F, Alvarez-Bolad G, Meyer BI, Roth KA, Gruss P . 1998 Cell 94: 727–737
Eisen MB, Spellman PT, Brown PO, Botstein D . 1998 Proc. Natl. Acad. Sci. USA 95: 14863–14868
El-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, Vogelstein B . 1992 Nat. Genet. 1: 45–49
Gostissa M, Hengstermann A, Fogal V, Sandy P, Schwarz SE, Scheffner M, Sal GD . 1999 EMBO J. 18: 6462–6471
Jimenez GS, Nister M, Stommel JM, Beeche M, Barcarse EA, Zhang X-Q, O'Gorman S, Wahl GM . 2000 Nat. Genet. 26: 37–43
Kaminski N, Allard J, Heller RA . 2000a Ann. N.Y. Acad. Sci. 919: 1–8
Kaminski N, Allard JD, Pittet JF, Zuo F, Griffiths MJD, Morris D, Huang X, Sheppard D, Heller RA . 2000b Proc. Natl. Acad. Sci. USA 97: 1778–1783
Kannan K, Amariglio N, Rechavi G, Givol D . 2000 FEBS Lett. 470: 77–82
Kannan K, Amariglio N, Rechavi G, Jakob-Hirsch J, Kela I, Kaminski N, Getz G, Domany E, Givol D . 2001 Oncogene 20: 2225–2234
Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, McGarry TJ, Kirschner MW, Koths K, Kwiatkowski D, Williams LT . 1997 Science 278: 294–298
Kusano H, Shimizu S, Koya RC, Fujita H, Kamada S, Kuzumaki N, Tsujimoto Y . 2000 Oncogene 19: 4807–4814
Levine AJ . 1997 Cell 88: 323–331
Levy N, Yonish-Rouach E, Oren M, Kimchi A . 1993 Mol. Cell. Biol. 13: 7942–7952
Maxwell SA, Davis GE . 2000 Proc. Natl. Acad. Sci. USA 97: 13009–13014
Michalovitz D, Halevy O, Oren M . 1990 Cell 62: 671–680
Muller S, Berger M, Lehembre F, Seeler JS, Haupt Y, Dejean A . 2000 J Biol. Chem. 275: 13321–13329
Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y, Taya Y . 2000 Cell 102: 849–862
Owen-Scaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T, Roth JA, Deisseroth AB, Zhang W-W, Kruzel E, Radinsky R . 1995 Mol. Cell. Biol. 15: 3032–3040
Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B . 1997 Nature 389: 300–305
Rodriguez MS, Desterro JMP, Lain S, Midgley CA, Lane DP, Hay RT . 1999 EMBO J. 18: 6455–6461
Scherer SJ, Maier SM, Seifert M, Hanselmann RG, Zang KD, Muller-Hermeling HK, Angel P, Welter C, Schartl M . 2000 J. Biol. Chem. 275: 37469–37473
Shikama N, Lee CW, France S, Delavaine L, Lyon J, Krstic-Demonacos M, LaThangue NB . 1999 Mol. Cell 4: 365–376
Soengas MS, Alarcon RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, Lowe SW . 1999 Science 284: 156–159
Vousden KH . 2000 Cell 103: 691–694
Wang Y, Blandino G, Oren M, Givol D . 1998 Oncogene 17: 1923–1930
Yonish-Rouach E, Grunwald D, Wilder S, Kimchi A, May E, Lawrence J, May P, Oren M . 1993 Mol. Cell. Biol. 13: 1415–1423
Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M . 1991 Nature 352: 345–347
Yoshida H, Kong Y, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW . 1998 Cell 94: 739–750
Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B . 1999 Proc. Natl. Acad. Sci. USA 96: 14517–14522
Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH, Tom E, Mack DH, Levine AJ . 2000 Genes Dev. 14: 981–993
Acknowledgements
We thank Prof M Oren for providing us the M1 and LTR6 cell lines. We thank the Arison Dorsman family donation for the Center of DNA Chips in Pediatric Oncology. This work was supported in part by Yad Abraham Research Center for Cancer Diagnosis and Therapy and the Rich Foundation for Leukemia Research. G Rechavi holds the Gregorio and Dora Shapiro Chair for Hematologic Malignancies, Sackler School of Medicine, Tel Aviv University. We thank Eli Berkovich for helpful suggestions and Marilyn Safran from the Crown Human Genome Center of the Weizmann Institute for assistance.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kannan, K., Kaminski, N., Rechavi, G. et al. DNA microarray analysis of genes involved in p53 mediated apoptosis: activation of Apaf-1. Oncogene 20, 3449–3455 (2001). https://doi.org/10.1038/sj.onc.1204446
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204446
Keywords
This article is cited by
-
PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response
Nature Communications (2022)
-
The Relevance of SNPs at 3′UTR Region of CASP7 and miR-371b-5p Associated Diseases: A Computational Analysis
Cell Biochemistry and Biophysics (2020)
-
The multiple mechanisms that regulate p53 activity and cell fate
Nature Reviews Molecular Cell Biology (2019)
-
ERK mediated upregulation of death receptor 5 overcomes the lack of p53 functionality in the diaminothiazole DAT1 induced apoptosis in colon cancer models: efficiency of DAT1 in Ras-Raf mutated cells
Molecular Cancer (2016)
-
The DNA repair complex Ku70/86 modulates Apaf1 expression upon DNA damage
Cell Death & Differentiation (2011)