Constitutive mdmx Expression During Cell Growth, Differentiation, and DNA Damage

Jackson, Mark W.; Berberich, Steven J.
September 1999
DNA & Cell Biology;Sep99, Vol. 18 Issue 9, p693
Academic Journal
The mdmx gene was shown to possess high homology to the mdm-2 gene and to encode a protein that can bind p53 and block p53 transactivation. Because Mdm-2 protein blocks the growth-suppressive activity of the p53 tumor-suppressor protein through similar activities, we examined the expression patterns of mdmx to determine how MdmX expression correlates with p53 protein levels. In this study, the expression pattern and protein levels of mdmx were examined in a number of cell culture systems. Like mdm-2, mdmx gene expression was constitutive during serum deprivation/restimulation of murine fibroblasts and differentiation of either murine teratocarcinoma or preadipocyte cells. In contrast, whereas mdm-2 gene expression was induced after cisplatin damage to ovarian carcinoma cells, mdmx expression remained constitutive. Because p53 transactivation is critical following a genotoxic stress, we examined p53:MdmX complexes after in vitro DNA-PK phosphorylation, a posttranslational modification that blocks p53 association with Mdm-2. The DNA-PK phosphorylation of p53 was capable of inhibiting p53:MdmX association. Thus, whereas DNA damage does not regulate mdmx mRNA levels, posttranslational modifications induced during DNA damage may block p53:MdmX association in vivo. These results demonstrate that, in the cell lines examined, mdmx gene expression remains constitutive during cell proliferation and differentiation or following DNA damage. Taken together, the data suggest that cells retain a constant level of MdmX. Thus, in undamaged cells, there exists the potential for an MdmX:p53 reservoir.


Related Articles

  • Structure and function of adenosine receptors and their genes. Fredholm, Bertil B.; Arslan, Giulia; Halldner, Linda; Kull, Björn; Schulte, Gunnar; Wasserman, Wyeth // Naunyn-Schmiedeberg's Archives of Pharmacology;Nov2000, Vol. 362 Issue 4/5, p364 

    Four adenosine receptors have been cloned from many mammalian and some non-mammalian species. In each case the translated part of the receptor is encoded by two separate exons. Two separate promoters regulate the A1 receptor expression, and a similar situation may pertain also for the other...

  • Characterization of DNA binding, transcriptional activation, and regulated nuclear association of recombinant human NFATp. Kim, Loree J.; Ferguson, Heather A.; Seto, Anita G.; Goodrich, James A. // BMC Immunology;2000, Vol. 1, p1 

    Background: NFATp is one member of a family of transcriptional activators whose nuclear accumulation and hence transcriptional activity is regulated in mammalian cells. Human NFATp exists as a phosphoprotein in the cytoplasm of naive T cells. Upon antigen stimulation, NFATp is dephosphorylated,...

  • Construction and Stable Expression of a Truncated Human Receptor Tyrosine Kinase Ror1 (Ror1-ECD). Forouzesh, Flora; Tabarian, Samira Shakeri; Emami, Shaghayegh; Tehrani, Mahmood-Jeddi; Hadavi, Reza; Rabbani, Hodjattallah // Avicenna Journal of Medical Biotechnology;Jan-Mar2012, Vol. 4 Issue 1, p41 

    Expression of receptor tyrosine kinase Ror1 in a wide variety of cancers has emerged as a new era focusing on targeting this receptor in cancer therapy. Our preliminary results indicate the presence of a truncated transcript of Ror1 in tumor cells. The truncated Ror1 encompasses extracellular...

  • Characterization and Functional Assessment of Mouse PPARγ1 Promoter. Lachinani, Liana; Ghaedi, Kamran; Tanhaei, Somayeh; Salamian, Ahmad; Karamali, Fereshteh; Kiani-Esfahani, Abbas; Rabiee, Farzaneh; Yaghmaei, Parichehreh; Baharvand, Hossein; Nasr-Esfahani, Mohammad Hossein // Avicenna Journal of Medical Biotechnology;Oct-Dec2012, Vol. 4 Issue 4, p160 

    Background: Peroxisome Proliferator Activated Receptor gamma (PPARγ), a member of nuclear receptor superfamily, comprises two isoforms in mouse. These two isoforms are encoded by different mRNAs, which are arisen by alternative promoter usage. There are two promoter regions upstream of...

  • In vitro changes in human tenocyte cultures obtained from proximal biceps tendon: multiple passages result in changes in routine cell markers. Mazzocca, Augustus; Chowaniec, David; McCarthy, Mary; Beitzel, Knut; Cote, Mark; McKinnon, William; Arciero, Robert // Knee Surgery, Sports Traumatology, Arthroscopy;Sep2012, Vol. 20 Issue 9, p1666 

    Purpose: Results of in vitro cell models are commonly used to promote new therapies (e.g., platelet-rich plasma), and clinicians have to be aware of the specific limitations of such models. To gain a sufficient and effective cell load, many current in vitro models use cells multiplied through...

  • Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection. Lehmann, Jan; Retz, Margitta; Harder, Jürgen; Krams, Matthias; Kellner, Udo; Hartmann, Julia; Hohgräwe, Kerstin; Raffenberg, Uta; Gerber, Martin; Loch, Tillmann; Weichert-Jacobsen, Klaus; Stöckle, Michael // BMC Infectious Diseases;2002, Vol. 2 Issue 1, p20 

    Background: Constitutive expression and localization of antimicrobial human β-defensin-1 (HBD-1) in human kidneys as a potential mechanism of antimicrobial defense has been previously reported. Inducible expression of human β-defensin-2 (HBD-2) has been described in various epithelial...

  • Baculovirus solves a complex problem. Roy, Polly // Nature Biotechnology;Dec2004, Vol. 22 Issue 12, p1527 

    The article presents information about an improved method for expressing multiple genes from a single baculovirus vector, which facilitates the production of protein complexes. Although some protein complexes can be readily isolated owing to their abundance in cells, many other interesting and...

  • Development of an osteoblast-based 3D continuous-perfusion microfluidic system for drug screening. Kihoon Jang; Sato, Kae; Igawa, Kazuyo; Ung-il Chung; Kitamori, Takehiko // Analytical & Bioanalytical Chemistry;Feb2008, Vol. 390 Issue 3, p825 

    In this work, we demonstrated that biological cells could be cultured in a continuous-perfusion glass microchip system for drug screening. We used mouse Col1a1GFP MC-3T3 E1 osteoblastic cells, which have a marker gene system expressing green fluorescent protein (GFP) under the control of...

  • Online imaging of initial DNA damages at the PTB microbeam. Giesen, U.; Langner, F.; Mielke, C.; Mosconi, M.; Dirks, W. G. // Radiation Protection Dosimetry;Feb2011, Vol. 143 Issue 2-4, p349 

    In an inter-disciplinary collaboration of Physikalisch-Technische Bundesanstalt (PTB), German Collection of Microorganisms and Cell Cultures (DSMZ) and Heinrich-Heine University, live-cell imaging has been established at the charged-particle microbeam facility of PTB. Candidate genes...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics