Cancer Research The Future of Cancer Research: Science and Patient Impact Tumor Immunology: New Perspectives
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
[Cancer Research 59, 6091-6096, December 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Riemenschneider, M. J.
Right arrow Articles by Reifenberger, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Riemenschneider, M. J.
Right arrow Articles by Reifenberger, G.
[Cancer Research 59, 6091-6096, December 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Amplification and Overexpression of the MDM4 (MDMX) Gene from 1q32 in a Subset of Malignant Gliomas without TP53 Mutation or MDM2 Amplification1

Markus J. Riemenschneider2, Rainer Büschges2, Marietta Wolter, Julia Reifenberger, Jan Boström, Jürgen A. Kraus, Uwe Schlegel and Guido Reifenberger3

Departments of Neuropathology [M. J. R., R. B., M. W., G. R.], Neurosurgery [J. B.], and Neurology [J. A. K., U. S.], University of Bonn Medical Center, D-53105 Bonn, and Department of Dermatology, Heinrich-Heine-University, D-40225 Düsseldorf [J. R.], Germany

We have previously reported on the amplification and overexpression of the MDM2 proto-oncogene in a subset of malignant gliomas without TP53 mutation (G. Reifenberger et al., Cancer Res., 53: 2736–2739, 1993). Here, we show that the MDM4 (MDMX) gene located on 1q32 is a further target for amplification in malignant gliomas. MDM4 codes for a Mdm2-related protein that can bind to p53 and inhibits p53-mediated transcriptional transactivation. We investigated a series of 208 gliomas (106 glioblastomas, 46 anaplastic gliomas, and 56 low-grade gliomas) and identified 5 tumors (4 glioblastomas and 1 anaplastic oligodendroglioma) with MDM4 amplification and overexpression. Several other genes from 1q32 were found to be coamplified with MDM4, such as GAC1 in five tumors, REN in four tumors, and RBBP5 in three tumors. Additional analyses revealed that the malignant gliomas with MDM4 amplification and overexpression carried neither mutations in conserved regions of the TP53 gene nor amplification of the MDM2 gene. Taken together, our data indicate that amplification and overexpression of MDM4 is a novel molecular mechanism by which a small fraction of human malignant gliomas escapes p53-dependent growth control.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
V. Lopez-Pajares, M. M. Kim, and Z.-M. Yuan
Phosphorylation of MDMX Mediated by Akt Leads to Stabilization and Induces 14-3-3 Binding
J. Biol. Chem., May 16, 2008; 283(20): 13707 - 13713.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Veerakumarasivam, H. E. Scott, S.-F. Chin, A. Warren, M. J. Wallard, D. Grimmer, K. Ichimura, C. Caldas, V. P. Collins, D. E. Neal, et al.
High-Resolution Array-Based Comparative Genomic Hybridization of Bladder Cancers Identifies Mouse Double Minute 4 (MDM4) as an Amplification Target Exclusive of MDM2 and TP53
Clin. Cancer Res., May 1, 2008; 14(9): 2527 - 2534.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
D. M. Gilkes, Y. Pan, D. Coppola, T. Yeatman, G. W. Reuther, and J. Chen
Regulation of MDMX Expression by Mitogenic Signaling
Mol. Cell. Biol., March 15, 2008; 28(6): 1999 - 2010.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Z. Matijasevic, H. A. Steinman, K. Hoover, and S. N. Jones
MdmX Promotes Bipolar Mitosis To Suppress Transformation and Tumorigenesis in p53-Deficient Cells and Mice
Mol. Cell. Biol., February 15, 2008; 28(4): 1265 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Jin, S. X. Zeng, X.-X. Sun, H. Lee, C. Blattner, Z. Xiao, and H. Lu
MDMX Promotes Proteasomal Turnover of p21 at G1 and Early S Phases Independently of, but in Cooperation with, MDM2
Mol. Cell. Biol., February 15, 2008; 28(4): 1218 - 1229.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al.
Malignant astrocytic glioma: genetics, biology, and paths to treatment
Genes & Dev., November 1, 2007; 21(21): 2683 - 2710.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Hu, D. M. Gilkes, and J. Chen
Efficient p53 Activation and Apoptosis by Simultaneous Disruption of Binding to MDM2 and MDMX
Cancer Res., September 15, 2007; 67(18): 8810 - 8817.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. V. Wang, M. Wade, E. Wong, Y.-C. Li, L. W. Rodewald, and G. M. Wahl
Quantitative analyses reveal the importance of regulated Hdmx degradation for P53 activation
PNAS, July 24, 2007; 104(30): 12365 - 12370.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J.-C. W. Marine, M. A. Dyer, and A. G. Jochemsen
MDMX: from bench to bedside
J. Cell Sci., February 1, 2007; 120(3): 371 - 378.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Okamoto, K. Kashima, Y. Pereg, M. Ishida, S. Yamazaki, A. Nota, A. Teunisse, D. Migliorini, I. Kitabayashi, J.-C. Marine, et al.
DNA Damage-Induced Phosphorylation of MdmX at Serine 367 Activates p53 by Targeting MdmX for Mdm2-Dependent Degradation
Mol. Cell. Biol., November 1, 2005; 25(21): 9608 - 9620.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Giglio, F. Mancini, F. Gentiletti, G. Sparaco, L. Felicioni, F. Barassi, C. Martella, A. Prodosmo, S. Iacovelli, F. Buttitta, et al.
Identification of an Aberrantly Spliced Form of HDMX in Human Tumors: A New Mechanism for HDM2 Stabilization
Cancer Res., November 1, 2005; 65(21): 9687 - 9694.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. A. Freije, F. E. Castro-Vargas, Z. Fang, S. Horvath, T. Cloughesy, L. M. Liau, P. S. Mischel, and S. F. Nelson
Gene Expression Profiling of Gliomas Strongly Predicts Survival
Cancer Res., September 15, 2004; 64(18): 6503 - 6510.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. V. Gurova, J. E. Hill, O. V. Razorenova, P. M. Chumakov, and A. V. Gudkov
p53 Pathway in Renal Cell Carcinoma Is Repressed by a Dominant Mechanism
Cancer Res., March 15, 2004; 64(6): 1951 - 1958.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Mancini, F. Gentiletti, M. D'Angelo, S. Giglio, S. Nanni, C. D'Angelo, A. Farsetti, G. Citro, A. Sacchi, A. Pontecorvi, et al.
MDM4 (MDMX) Overexpression Enhances Stabilization of Stress-induced p53 and Promotes Apoptosis
J. Biol. Chem., February 27, 2004; 279(9): 8169 - 8180.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
K. Onel and C. Cordon-Cardo
MDM2 and Prognosis
Mol. Cancer Res., January 1, 2004; 2(1): 1 - 8.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Chavez-Reyes, J. M. Parant, L. L. Amelse, R. M. de Oca Luna, S. J. Korsmeyer, and G. Lozano
Switching Mechanisms of Cell Death in mdm2- and mdm4-null Mice by Deletion of p53 Downstream Targets
Cancer Res., December 15, 2003; 63(24): 8664 - 8669.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
T. Iwakuma and G. Lozano
MDM2, An Introduction
Mol. Cancer Res., December 1, 2003; 1(14): 993 - 1000.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. de Graaf, N. A. Little, Y. F. M. Ramos, E. Meulmeester, S. J. F. Letteboer, and A. G. Jochemsen
Hdmx Protein Stability Is Regulated by the Ubiquitin Ligase Activity of Mdm2
J. Biol. Chem., October 3, 2003; 278(40): 38315 - 38324.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. M. Backlund, B. R. Nilsson, H. M. Goike, E. E. Schmidt, L. Liu, K. Ichimura, and V. P. Collins
Short Postoperative Survival for Glioblastoma Patients with a Dysfunctional Rb1 Pathway in Combination with No Wild-type PTEN
Clin. Cancer Res., September 15, 2003; 9(11): 4151 - 4158.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
Y. YANG and X. YU
Regulation of apoptosis: the ubiquitous way
FASEB J, May 1, 2003; 17(8): 790 - 799.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. C. Badciong and A. L. Haas
MdmX Is a RING Finger Ubiquitin Ligase Capable of Synergistically Enhancing Mdm2 Ubiquitination
J. Biol. Chem., December 13, 2002; 277(51): 49668 - 49675.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. A. Finch, D. B. Donoviel, D. Potter, M. Shi, A. Fan, D. D. Freed, C.-y. Wang, B. P. Zambrowicz, R. Ramirez-Solis, A. T. Sands, et al.
mdmx Is a Negative Regulator of p53 Activity in Vivo
Cancer Res., June 1, 2002; 62(11): 3221 - 3225.
[Abstract] [Full Text] [PDF]

Home page
 Neuro OncolHome page
M. T. Giordana, D. Duo, S. Gasverde, E. Trevisan, A. Boghi, I. Morra, L. Pradotto, A. Mauro, and A. Chio
MDM2 overexpression is associated with short survival in adults with medulloblastoma
Neuro-oncol, April 1, 2002; 4(2): 115 - 122.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
P. Chen, K. Aldape, J. K. Wiencke, K. T. Kelsey, R. Miike, R. L. Davis, J. Liu, A. Kesler-Diaz, M. Takahashi, and M. Wrensch
Ethnicity Delineates Different Genetic Pathways in Malignant Glioma
Cancer Res., May 1, 2001; 61(10): 3949 - 3954.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
Y. F. M. Ramos, R. Stad, J. Attema, L. T. C. Peltenburg, A. J. van der Eb, and A. G. Jochemsen
Aberrant Expression of HDMX Proteins in Tumor Cells Correlates with Wild-Type p53
Cancer Res., March 1, 2001; 61(5): 1839 - 1842.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
D. S. Rickman, R. Tyagi, X.-X. Zhu, M. P. Bobek, S. Song, M. Blaivas, D. E. Misek, M. A. Israel, D. M. Kurnit, D. A. Ross, et al.
The Gene for the Axonal Cell Adhesion Molecule TAX-1 Is Amplified and Aberrantly Expressed in Malignant Gliomas
Cancer Res., March 1, 2001; 61(5): 2162 - 2168.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M. W. Jackson, M. S. Lindstrom, and S. J. Berberich
MdmX Binding to ARF Affects Mdm2 Protein Stability and p53 Transactivation
J. Biol. Chem., June 29, 2001; 276(27): 25336 - 25341.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.