Nucleic Acids Research, 1993, Vol. 21, No. 14 3167-3174
© 1993
MOLECULAR BIOLOGY |
Activation of the cryptic DNA binding function of mutant forms of p53
Cancer Research Campaign Laboratories Dundee DD1 4HN, UK 1MRC Protein Phosphorylation Unit, Department of Biochemistry Dundee DD1 4HN, UK
*To whom correspondence should be addressed
Received April 26, 1993. Revised June 9, 1993. Accepted June 9, 1993.
Wild type p53 assembles into a latent multiprotein complex which can be activated for sequence-specific DNA binding in vitro by proteins targeting the carboxy terminal domain. Using an optimized system coupling the post-translational modification of wild type p53 to activation of sequence specific DNA binding, we examined the aftects of common mutations on the cryptic DNA binding function of p53. Two mutant forms of p53 were shown to be eftlciently converted from the latent state by PAb421 and DnaK, but were defective in activation by casein kinase II, Indicating that mutant p53 may not be receptive to allosteric regulation by casein kinase II phosphorylation. A reactive sulfhydryl group is absolutely required for DNA binding by wlid type and mutant forms of p53 once converted to the activated state. Together, these data show that some mutant forms of p53 harbour the wild-type machinery required to engage in sequence-specific DNA binding and define a signalling pathway whose inactivation may directly result in a loss of p53 function.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. J.-L. RILEY, L. A. CASSIDAY, A. KUMAR, and L. J. MAHER III Recognition of RNA by the p53 tumor suppressor protein in the yeast three-hybrid system. RNA, April 1, 2006; 12(4): 620 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schneider-Merck, Y. Pohnke, R. Kempf, M. Christian, J. J. Brosens, and B. Gellersen Physical Interaction and Mutual Transrepression between CCAAT/Enhancer-binding Protein {beta} and the p53 Tumor Suppressor J. Biol. Chem., January 6, 2006; 281(1): 269 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.P. LANE Exploiting the p53 Pathway for the Diagnosis and Therapy of Human Cancer Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 489 - 497. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Pohnke, T. Schneider-Merck, J. Fahnenstich, R. Kempf, M. Christian, K. Milde-Langosch, J. J. Brosens, and B. Gellersen Wild-Type p53 Protein Is Up-Regulated upon Cyclic Adenosine Monophosphate-Induced Differentiation of Human Endometrial Stromal Cells J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5233 - 5244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lane p53 from pathway to therapy Carcinogenesis, July 1, 2004; 25(7): 1077 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Brash and P. A. Havre New careers for antioxidants PNAS, October 29, 2002; 99(22): 13969 - 13971. [Full Text] [PDF]
|
|
|
|
|
|
Q. Yang, R. Zhang, X. W. Wang, E. A. Spillare, S. P. Linke, D. Subramanian, J. D. Griffith, J. L. Li, I. D. Hickson, J. C. Shen, et al. The Processing of Holliday Junctions by BLM and WRN Helicases Is Regulated by p53 J. Biol. Chem., August 23, 2002; 277(35): 31980 - 31987. [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. S. Sullivan and J. M. Pipas T Antigens of Simian Virus 40: Molecular Chaperones for Viral Replication and Tumorigenesis Microbiol. Mol. Biol. Rev., June 1, 2002; 66(2): 179 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sigal and V. Rotter Oncogenic Mutations of the p53 Tumor Suppressor: The Demons of the Guardian of the Genome Cancer Res., December 1, 2000; 60(24): 6788 - 6793. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Gu, D. Chen, J. Rosenblum, R. M. Rubin, and Z.-M. Yuan Identification of a Sequence Element from p53 That Signals for Mdm2-Targeted Degradation Mol. Cell. Biol., February 15, 2000; 20(4): 1243 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, M. Ljungman, and J. E. Dixon The Human Cdc14 Phosphatases Interact with and Dephosphorylate the Tumor Suppressor Protein p53 J. Biol. Chem., January 28, 2000; 275(4): 2410 - 2414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kim, A. J. Raffo, P. W. Brandt-Rauf, M. R. Pincus, R. Monaco, P. Abarzua, and R. L. Fine Conformational and Molecular Basis for Induction of Apoptosis by a p53 C-terminal Peptide in Human Cancer Cells J. Biol. Chem., December 3, 1999; 274(49): 34924 - 34931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Meplan, K. Mann, and P. Hainaut Cadmium Induces Conformational Modifications of Wild-type p53 and Suppresses p53 Response to DNA Damage in Cultured Cells J. Biol. Chem., October 29, 1999; 274(44): 31663 - 31670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fojta Effect of p53 Protein Redox States on Binding to Supercoiled and Linear DNA J. Biol. Chem., September 3, 1999; 274(36): 25749 - 25755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Selivanova, L. Ryabchenko, E. Jansson, V. Iotsova, and K. G. Wiman Reactivation of Mutant p53 through Interaction of a C-Terminal Peptide with the Core Domain Mol. Cell. Biol., May 1, 1999; 19(5): 3395 - 3402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Webster and N. D. Perkins Transcriptional Cross Talk between NF-kappa B and p53 Mol. Cell. Biol., May 1, 1999; 19(5): 3485 - 3495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Huang, W.-Y. Ma, A. Maxiner, Y. Sun, and Z. Dong p38 Kinase Mediates UV-induced Phosphorylation of p53 Protein at Serine 389 J. Biol. Chem., April 30, 1999; 274(18): 12229 - 12235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Janus, N. Albrechtsen, U. Knippschild, L. Wiesmuller, F. Grosse, and W. Deppert Different Regulation of the p53 Core Domain Activities 3'-to-5' Exonuclease and Sequence-Specific DNA Binding Mol. Cell. Biol., March 1, 1999; 19(3): 2155 - 2168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-y. Tang, K. Zhao, J. F. Pizzolato, M. Fonarev, J. C. Langer, and J. J. Manfredi Constitutive Expression of the Cyclin-dependent Kinase Inhibitor p21 Is Transcriptionally Regulated by the Tumor Suppressor Protein p53 J. Biol. Chem., October 30, 1998; 273(44): 29156 - 29163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Giaccia and M. B. Kastan The complexity of p53 modulation: emerging patterns from divergent signals Genes & Dev., October 1, 1998; 12(19): 2973 - 2983. [Full Text]
|
|
|
|
|
|
H.-H. Wu and J. Momand Pyrrolidine Dithiocarbamate Prevents p53 Activation and Promotes p53 Cysteine Residue Oxidation J. Biol. Chem., July 24, 1998; 273(30): 18898 - 18905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. F. Muller-Tiemann, T. D. Halazonetis, and J. J. Elting Identification of an additional negative regulatory region for p53 sequence-specific DNA binding PNAS, May 26, 1998; 95(11): 6079 - 6084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Chernov, C. V. Ramana, V. V. Adler, and G. R. Stark Stabilization and activation of p53 are regulated independently by different phosphorylation events PNAS, March 3, 1998; 95(5): 2284 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Whitesell, P. D. Sutphin, E. J. Pulcini, J. D. Martinez, and P. H. Cook The Physical Association of Multiple Molecular Chaperone Proteins with Mutant p53 Is Altered by Geldanamycin, an hsp90-Binding Agent Mol. Cell. Biol., March 1, 1998; 18(3): 1517 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Fourie, T. R. Hupp, D. P. Lane, B.-C. Sang, M. S. Barbosa, J. F. Sambrook, and M.-J. H. Gething HSP70 Binding Sites in the Tumor Suppressor Protein p53 J. Biol. Chem., August 1, 1997; 272(31): 19471 - 19479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Adler, M. R. Pincus, T. Minamoto, S. Y. Fuchs, M. J. Bluth, P. W. Brandt-Rauf, F. K. Friedman, R. C. Robinson, J. M. Chen, X. W. Wang, et al. Conformation-dependent phosphorylation of p53 PNAS, March 4, 1997; 94(5): 1686 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hansen, C. A. Midgley, D. P. Lane, B. C. Freeman, R. I. Morimoto, and T. R. Hupp Modification of Two Distinct COOH-terminal Domains Is Required for Murine p53 Activation by Bacterial Hsp70 J. Biol. Chem., November 29, 1996; 271(48): 30922 - 30928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Friedlander, Y. Legros, T. Soussi, and C. Prives Regulation of Mutant p53 Temperature-sensitive DNA Binding J. Biol. Chem., October 11, 1996; 271(41): 25468 - 25478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L J Ko and C Prives p53: puzzle and paradigm. Genes & Dev., May 1, 1996; 10(9): 1054 - 1072. [PDF]
|
|
|
|
|
|
S. Hansen, T. R. Hupp, and D. P. Lane Allosteric Regulation of the Thermostability and DNA Binding Activity of Human p53 by Specific Interacting Proteins J. Biol. Chem., February 16, 1996; 271(7): 3917 - 3924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Russo, N. Zambrano, F. Esposito, R. Ammendola, F. Cimino, M. Fiscella, J. Jackman, P. M. O'Connor, C. W. Anderson, and E. Appella A p53-independent Pathway for Activation of WAF1/CIP1 Expression Following Oxidative Stress J. Biol. Chem., December 8, 1995; 270(49): 29386 - 29391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Hupp and D. P. Lane Two Distinct Signaling Pathways Activate the Latent DNA Binding Function of p53 in a Casein Kinase II-independent Manner J. Biol. Chem., July 28, 1995; 270(30): 18165 - 18174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-J. Gething, S. Blond-Elguindi, J. Buchner, A. Fourie, G. Knarr, S. Modrow, L. Nanu, M. Segal, and J. Sambrook Binding Sites for Hsp70 Molecular Chaperones in Natural Proteins Cold Spring Harb Symp Quant Biol, January 1, 1995; 60(0): 417 - 428. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Hartwell and M. Kastan Cell cycle control and cancer Science, December 16, 1994; 266(5192): 1821 - 1828. [Abstract] [PDF]
|
|
|
|
|
|
T.R. Hupp and D.P. Lane Regulation of the Cryptic Sequence-specific DNA-binding Function of p53 by Protein Kinases Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 195 - 206. [Abstract] [PDF]
|
|
|
|
|
|
Y Wang, M Reed, P Wang, J E Stenger, G Mayr, M E Anderson, J F Schwedes, and P Tegtmeyer p53 domains: identification and characterization of two autonomous DNA-binding regions. Genes & Dev., December 1, 1993; 7(12b): 2575 - 2586. [Abstract] [PDF]
|
|
|
|
|
|
C. Cain, S. Miller, J. Ahn, and C. Prives The N Terminus of p53 Regulates Its Dissociation from DNA J. Biol. Chem., December 15, 2000; 275(51): 39944 - 39953. [Abstract] [Full Text] [PDF]
|
|