| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print May 29, 2001
Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115
Corresponding Author: zyuan{at}hsph.harvard.edu
Under normal conditions, tumor suppressor protein p53 exists in the cell in its latent form and is unable to function as a transcription factor. Allosteric model of p53 regulation postulates that the extreme portion of p53 carboxyl terminus (aa 364-393) binds to the core domain of the protein, thereby abrogating specific DNA binding in that region. In this study we propose an alternative mechanism of p53 functional regulation, which involves a separate molecule acting in trans to inhibit p53 transcriptional activity. Through the use of chimeric proteins of p53, p63ƒ× and p73ƒÒ, we show that the extreme c-terminal domain of p53 exerts a powerful and specific inhibitory effect on the p73- and p63-driven expression of a reporter gene. Moreover, fusion of p53 extreme c-terminus to a completely unrelated transcriptional activator Gal4-VP16 also results in significant inhibition of transactivation activity. Since p73, p63 or Gal4-VP16 can not associate with any part of the p53 molecule, we conclude that p53(aa 364-393) represses transcriptional activity of chimeric proteins and p53 itself through the binding of external negative modulator(s) in that region, and not by the allosteric mechanism of regulation. In accordance with the ¡§distinct inhibitor¡¨ hypothesis, activity of wild type p53 is substantially increased by overexpression of chimeric proteins bearing p53(aa364-393), which might be due to the competitive removal of transcriptional inhibitor(s). Our findings provide basis for the identification of such negative modulators of p53 transcriptional activity.
J. Biol. Chem, 10.1074/jbc.M102400200
Submitted on March 16, 2001
Revised on May 29, 2001
Accepted on May 25, 2001
Evidence for a distinct inhibitory factor in the regulation of p53 functional activity
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Tang and C. Eng PTEN Autoregulates Its Expression by Stabilization of p53 in a Phosphatase-Independent Manner Cancer Res., January 15, 2006; 66(2): 736 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Y. Zhao, J. Liu, G. S. Sidhu, Y. Niu, Y. Liu, R. Wang, and D. Liao Negative Regulation of p53 Functions by Daxx and the Involvement of MDM2 J. Biol. Chem., November 26, 2004; 279(48): 50566 - 50579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tomasini, A. A. Samir, A. Carrier, D. Isnardon, B. Cecchinelli, S. Soddu, B. Malissen, J.-C. Dagorn, J. L. Iovanna, and N. J. Dusetti TP53INP1s and Homeodomain-interacting Protein Kinase-2 (HIPK2) Are Partners in Regulating p53 Activity J. Biol. Chem., September 26, 2003; 278(39): 37722 - 37729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Davis, Y. Dong, and R. H. Weiss Overexpression of p73 causes apoptosis in vascular smooth muscle cells Am J Physiol Cell Physiol, January 1, 2003; 284(1): C16 - C23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wong, P.-X. Li, and H. J. Klamut A Novel p53 Transcriptional Repressor Element (p53TRE) and the Asymmetrical Contribution of Two p53 Binding Sites Modulate the Response of the Placental Transforming Growth Factor-beta Promoter to p53 J. Biol. Chem., July 12, 2002; 277(29): 26699 - 26707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yan, H. Wang, and D. D. Boyd ATF3 Represses 72-kDa Type IV Collagenase (MMP-2) Expression by Antagonizing p53-dependent trans-Activation of the Collagenase Promoter J. Biol. Chem., March 22, 2002; 277(13): 10804 - 10812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mendoza-Alvarez and R. Alvarez-Gonzalez Regulation of p53 Sequence-specific DNA-binding by Covalent Poly(ADP-ribosyl)ation J. Biol. Chem., September 21, 2001; 276(39): 36425 - 36430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Klein, E. Planker, T. Diercks, H. Kessler, K.-P. Kunkele, K. Lang, S. Hansen, and M. Schwaiger NMR Spectroscopy Reveals the Solution Dimerization Interface of p53 Core Domains Bound to Their Consensus DNA J. Biol. Chem., December 21, 2001; 276(52): 49020 - 49027. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
