| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20892
The possibility that appropriately designed chemotherapy could act selectively against p53-defective tumor cells was explored in MCF-7 human breast cancer cells. These cells were chosen because they have normal p53 function but are representative of a tumor cell type that does not readily undergo p53-dependent apoptosis. Two sublines (MCF-7/E6 and MCF-7/mu-p53) were established in which p53 function was disrupted by transfection with either the human papillomavirus type-16 E6 gene or a dominant-negative mutant p53 gene. p53 function in MCF-7/E6 and MCF-7/mu-p53 cells was defective relative to control cells in that there were no increases in p53 or p21Waf1/Cip1 protein levels and no G1 arrest following exposure to ionizing radiation. Survival assays showed that p53 disruption sensitized MCF-7 cells to cisplatin (CDDP) but not to several other DNA-damaging agents. CDDP sensitization was not limited to MCF-7 cells since p53 disruption in human colon carcinoma RKO cells also enhanced sensitivity to CDDP. Contrary to the other DNA-damaging agents tested, CDDP-induced DNA lesions are repaired extensively by nucleotide excision, and in agreement with a defect in this process, MCF-7/E6 and MCF-7/mu-p53 cells exhibited a reduced ability to repair a CDDP-damaged chloramphenicol acetyltransferase-reporter plasmid transfected into the cells. Therefore, we attributed the increased CDDP sensitivity of MCF-7 cells with disrupted p53 to defects in G1 checkpoint control, nucleotide excision repair, or both. The G2 checkpoint inhibitor pentoxifylline exhibited synergism with CDDP in killing MCF-7/E6 cells but did not affect sensitivity of the control cells. Moreover, pentoxifylline inhibited G2 checkpoint function to a greater extent in MCF-7/E6 than in the parental cells. These results suggested that, in the absence of p53 function, cancer cells are more vulnerable to G2 checkpoint abrogators. Our results show that a combination of CDDP and pentoxifylline is capable of synergistic and preferential killing of p53-defective tumor cells that do not readily undergo apoptosis.
1 D. J. R. is a Howard Hughes Medical Institute Research Scholar at the NIH.
2 To whom requests for reprints should be addressed, at Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Room 5C-19, Bldg. 37, National Cancer Institute, NIH, Bethesda, MD 20892.
Received 1/17/95. Accepted 3/ 6/95.
This article has been cited by other articles:
|
|
 |
|
  H.-W. Lo, L. Stephenson, X. Cao, M. Milas, R. Pollock, and F. Ali-Osman Identification and Functional Characterization of the Human Glutathione S-Transferase P1 Gene as a Novel Transcriptional Target of the p53 Tumor Suppressor Gene Mol. Cancer Res., May 1, 2008; 6(5): 843 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Levesque, A. A. Fanous, A. Poh, and A. Eastman Defective p53 signaling in p53 wild-type tumors attenuates p21waf1 induction and cyclin B repression rendering them sensitive to Chk1 inhibitors that abrogate DNA damage-induced S and G2 arrest Mol. Cancer Ther., February 1, 2008; 7(2): 252 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bhana and D. R. Lloyd The role of p53 in DNA damage-mediated cytotoxicity overrides its ability to regulate nucleotide excision repair in human fibroblasts Mutagenesis, January 1, 2008; 23(1): 43 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Levesque and A. Eastman p53-based cancer therapies: is defective p53 the Achilles heel of the tumor? Carcinogenesis, January 1, 2007; 28(1): 13 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Fishel, Y. He, M. L. Smith, and M. R. Kelley Manipulation of Base Excision Repair to Sensitize Ovarian Cancer Cells to Alkylating Agent Temozolomide Clin. Cancer Res., January 1, 2007; 13(1): 260 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Afshar, N. Jelluma, X. Yang, D. Basila, N. D. Arvold, A. Karlsson, G. L. Yount, T. B. Dansen, E. Koller, and D. A. Haas-Kogan Radiation-Induced Caspase-8 Mediates p53-Independent Apoptosis in Glioma Cells. Cancer Res., April 15, 2006; 66(8): 4223 - 4232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Sturgeon, Z. A. Knight, K. M. Shokat, and M. Roberge Effect of combined DNA repair inhibition and G2 checkpoint inhibition on cell cycle progression after DNA damage. Mol. Cancer Ther., April 1, 2006; 5(4): 885 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Koblish, S. Zhao, C. F. Franks, R. R. Donatelli, R. M. Tominovich, L. V. LaFrance, K. A. Leonard, J. M. Gushue, D. J. Parks, R. R. Calvo, et al. Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo Mol. Cancer Ther., January 1, 2006; 5(1): 160 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Ferguson and D. H. Oh Proficient Global Nucleotide Excision Repair in Human Keratinocytes but not in Fibroblasts Deficient in p53 Cancer Res., October 1, 2005; 65(19): 8723 - 8729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Bauer, D. K. Trask, B. Kumar, G. Los, J. Castro, J. Shin-Jung Lee, J. Chen, S. Wang, C. R. Bradford, and T. E. Carey Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL Mol. Cancer Ther., July 1, 2005; 4(7): 1096 - 1104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Chu, J. Barkinge, S. Hawkins, R. Gudi, R. Salgia, and P. V.S. Kanteti Expression of Siva-1 Protein or Its Putative Amphipathic Helical Region Enhances Cisplatin-Induced Apoptosis in Breast Cancer Cells: Effect of Elevated Levels of BCL-2 Cancer Res., June 15, 2005; 65(12): 5301 - 5309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Jackson, M. K. Agarwal, J. Yang, P. Bruss, T. Uchiumi, M. L. Agarwal, G. R. Stark, and W. R. Taylor, p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2 J. Cell Sci., May 1, 2005; 118(9): 1821 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Karjala, Q. Chan, E. Manzo, R. J. Andersen, and M. Roberge Ceratamines, Structurally Simple Microtubule-Stabilizing Antimitotic Agents with Unusual Cellular Effects Cancer Res., April 15, 2005; 65(8): 3040 - 3043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wesierska-Gadek, M. Gueorguieva, and M. Horky Roscovitine-induced up-regulation of p53AIP1 protein precedes the onset of apoptosis in human MCF-7 breast cancer cells Mol. Cancer Ther., January 1, 2005; 4(1): 113 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Essmann, I. H. Engels, G. Totzke, K. Schulze-Osthoff, and R. U. Janicke Apoptosis Resistance of MCF-7 Breast Carcinoma Cells to Ionizing Radiation Is Independent of p53 and Cell Cycle Control but Caused by the Lack of Caspase-3 and a Caffeine-Inhibitable Event Cancer Res., October 1, 2004; 64(19): 7065 - 7072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. P. Lin, M. F. Belcourt, J. G. Cory, and A. C. Sartorelli Stable Suppression of the R2 Subunit of Ribonucleotide Reductase by R2-targeted Short Interference RNA Sensitizes p53(-/-) HCT-116 Colon Cancer Cells to DNA-damaging Agents and Ribonucleotide Reductase Inhibitors J. Biol. Chem., June 25, 2004; 279(26): 27030 - 27038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Crescenzi, L. Varriale, M. Iovino, A. Chiaviello, B. M. Veneziani, and G. Palumbo Photodynamic therapy with indocyanine green complements and enhances low-dose cisplatin cytotoxicity in MCF-7 breast cancer cells Mol. Cancer Ther., May 1, 2004; 3(5): 537 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Marabese, F. Vikhanskaya, C. Rainelli, T. Sakai, and M. Broggini DNA damage induces transcriptional activation of p73 by removing C-EBP{alpha} repression on E2F1 Nucleic Acids Res., November 15, 2003; 31(22): 6624 - 6632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schild-Poulter, A. Shih, N. C. Yarymowich, and R. J. G. Hache Down-Regulation of Histone H2B by DNA-Dependent Protein Kinase in Response to DNA Damage through Modulation of Octamer Transcription Factor 1 Cancer Res., November 1, 2003; 63(21): 7197 - 7205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Nowak, P. M. Price, and R. G. Schnellmann Lack of a functional p21WAF1/CIP1 gene accelerates caspase-independent apoptosis induced by cisplatin in renal cells Am J Physiol Renal Physiol, September 1, 2003; 285(3): F440 - F450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Clifford, M. Beljin, G. R. Stark, and W. R. Taylor G2 Arrest in Response to Topoisomerase II Inhibitors: The Role of p53 Cancer Res., July 15, 2003; 63(14): 4074 - 4081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Petit, D. J. Bearss, D. A. Troyer, R. M. Munoz, and J. J. Windle p53-independent Response to Cisplatin and Oxaliplatin in MMTV-ras Mouse Salivary Tumors Mol. Cancer Ther., February 1, 2003; 2(2): 165 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yoon, S. Liyanarachchi, F. A. Wright, R. Davuluri, J. C. Lockman, A. de la Chapelle, and N. S. Pellegata Gene expression profiling of isogenic cells with different TP53 gene dosage reveals numerous genes that are affected by TP53 dosage and identifies CSPG2 as a direct target of p53 PNAS, November 26, 2002; 99(24): 15632 - 15637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. R. Seo, M. R. Kelley, and M. L. Smith From the Cover: Selenomethionine regulation of p53 by a ref1-dependent redox mechanism PNAS, October 29, 2002; 99(22): 14548 - 14553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Eastman, E. A. Kohn, M. K. Brown, J. Rathman, M. Livingstone, D. H. Blank, and G. W. Gribble A Novel Indolocarbazole, ICP-1, Abrogates DNA Damage-induced Cell Cycle Arrest and Enhances Cytotoxicity: Similarities and Differences to the Cell Cycle Checkpoint Abrogator UCN-01 Mol. Cancer Ther., October 1, 2002; 1(12): 1067 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. W. Elmore, C. W. Rehder, X. Di, P. A. McChesney, C. K. Jackson-Cook, D. A. Gewirtz, and S. E. Holt Adriamycin-induced Senescence in Breast Tumor Cells Involves Functional p53 and Telomere Dysfunction J. Biol. Chem., September 13, 2002; 277(38): 35509 - 35515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Ma, J. Hu, D. J. Lindner, and D. V. Kalvakolanu Mutational Analysis of Human Thioredoxin Reductase 1. EFFECTS ON p53-MEDIATED GENE EXPRESSION AND INTERFERON AND RETINOIC ACID-INDUCED CELL DEATH J. Biol. Chem., June 14, 2002; 277(25): 22460 - 22468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ricordy, G. Gensabella, E. Cacci, and G. Augusti-Tocco Impairment of cell cycle progression by aflatoxin B1 in human cell lines Mutagenesis, May 1, 2002; 17(3): 241 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Wani, G. Wani, J. Yao, Q. Zhu, and A. A. Wani Human cells deficient in p53 regulated p21waf1/cip1 expression exhibit normal nucleotide excision repair of UV-induced DNA damage Carcinogenesis, March 1, 2002; 23(3): 403 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Loignon and E. A. Drobetsky The initiation of UV-induced G1 arrest in human cells is independent of the p53/p21/pRb pathway but can be attenuated through expression of the HPV E7 oncoprotein Carcinogenesis, January 1, 2002; 23(1): 35 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. T. Rundle, L. Xu, R. J. Andersen, and M. Roberge G2 DNA Damage Checkpoint Inhibition and Antimitotic Activity of 13-Hydroxy-15-oxozoapatlin J. Biol. Chem., December 14, 2001; 276(51): 48231 - 48236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Green, W. E. Antholine, S. J. Wong, D. R. Richardson, and C. R. Chitambar Inhibition of Malignant Cell Growth by 311, a Novel Iron Chelator of the Pyridoxal Isonicotinoyl Hydrazone Class: Effect on the R2 subunit of Ribonucleotide Reductase Clin. Cancer Res., November 1, 2001; 7(11): 3574 - 3579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Post, Y.-C. Weng, K. Cimprich, L. B. Chen, Y. Xu, and E. Y.-H. P. Lee Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G1/S checkpoint activation in response to DNA damage PNAS, October 25, 2001; (2001) 231364598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Robinson and D. S. Shewach Radiosensitization by Gemcitabine in p53 Wild-Type and Mutant MCF-7 Breast Carcinoma Cell Lines Clin. Cancer Res., August 1, 2001; 7(8): 2581 - 2589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Xu, C. L. Nutt, M. C. Zlatescu, M. Keeney, I. Chin-Yee, and J. G. Cairncross Inactivation of p53 Sensitizes U87MG Glioma Cells to 1,3-bis(2-Chloroethyl)-1-nitrosourea Cancer Res., May 1, 2001; 61(10): 4155 - 4159. [Abstract] [Full Text]
|
|
|
|
|
|
F. Vikhanskaya, S. Marchini, M. Marabese, E. Galliera, and M. Broggini p73{{alpha}} Overexpression Is Associated with Resistance to Treatment with DNA-damaging Agents in a Human Ovarian Cancer Cell Line Cancer Res., February 1, 2001; 61(3): 935 - 938. [Abstract] [Full Text]
|
|
|
|
|
|
J.-N. Li, M. Gorospe, F. J. Chrest, T. S. Kumaravel, M. K. Evans, W. F. Han, and E. S. Pizer Pharmacological Inhibition of Fatty Acid Synthase Activity Produces Both Cytostatic and Cytotoxic Effects Modulated by p53 Cancer Res., February 1, 2001; 61(4): 1493 - 1499. [Abstract] [Full Text]
|
|
|
|
|
|
X. Lin, K. Ramamurthi, M. Mishima, A. Kondo, R. D. Christen, and S. B. Howell p53 Modulates the Effect of Loss of DNA Mismatch Repair on the Sensitivity of Human Colon Cancer Cells to the Cytotoxic and Mutagenic Effects of Cisplatin Cancer Res., February 1, 2001; 61(4): 1508 - 1516. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. L. Smith, J. M. Ford, M. C. Hollander, R. A. Bortnick, S. A. Amundson, Y. R. Seo, C.-X. Deng, P. C. Hanawalt, and A. J. Fornace Jr. p53-Mediated DNA Repair Responses to UV Radiation: Studies of Mouse Cells Lacking p53, p21, and/or gadd45 Genes Mol. Cell. Biol., May 15, 2000; 20(10): 3705 - 3714. [Abstract] [Full Text]
|
|
|
|
|
|
M. A. Wani, Q. Zhu, M. El-Mahdy, S. Venkatachalam, and A. A. Wani Enhanced Sensitivity to anti-Benzo(a)pyrene-diol-epoxide DNA Damage Correlates with Decreased Global Genomic Repair Attributable to Abrogated p53 Function in Human Cells Cancer Res., April 1, 2000; 60(8): 2273 - 2280. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. E. Pestell, S. M. Hobbs, J. C. Titley, L. R. Kelland, and M. I. Walton Effect of p53 Status on Sensitivity to Platinum Complexes in a Human Ovarian Cancer Cell Line Mol. Pharmacol., March 1, 2000; 57(3): 503 - 511. [Abstract] [Full Text]
|
|
|
|
|
|
P. R. Graves, L. Yu, J. K. Schwarz, J. Gales, E. A. Sausville, P. M. O'Connor, and H. Piwnica-Worms The Chk1 Protein Kinase and the Cdc25C Regulatory Pathways Are Targets of the Anticancer Agent UCN-01 J. Biol. Chem., February 25, 2000; 275(8): 5600 - 5605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Coleman, J. Momand, and S. E. Kane Basic Fibroblast Growth Factor Sensitizes NIH 3T3 Cells to Apoptosis Induced by Cisplatin Mol. Pharmacol., February 1, 2000; 57(2): 324 - 333. [Abstract] [Full Text]
|
|
|
|
|
|
G. Aquilina, S. Ceccotti, S. Martinelli, S. Soddu, M. Crescenzi, P. Branch, P. Karran, and M. Bignami Mismatch Repair and p53 Independently Affect Sensitivity to N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea Clin. Cancer Res., February 1, 2000; 6(2): 671 - 680. [Abstract] [Full Text]
|
|
|
|
|
|
N. J. Donato, M. Perez, H. Kang, Z. H. Siddik, Y.-H. Ling, and R. Perez-Soler EGF Receptor and p21WAF1 Expression are Reciprocally Altered as ME-180 Cervical Carcinoma Cells Progress from High to Low Cisplatin Sensitivity Clin. Cancer Res., January 1, 2000; 6(1): 193 - 202. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Barrera-Hernandez, K. S. Park, A. Dace, Q. Zhan, and S.-y. Cheng Thyroid Hormone-Induced Cell Proliferation in GC Cells Is Mediated by Changes in G1 Cyclin/Cyclin-Dependent Kinase Levels and Activity Endocrinology, November 1, 1999; 140(11): 5267 - 5274. [Abstract] [Full Text]
|
|
|
|
|
|
J. Fan and J. R. Bertino Modulation of Cisplatinum Cytotoxicity by p53: Effect of p53-Mediated Apoptosis and DNA Repair Mol. Pharmacol., November 1, 1999; 56(5): 966 - 972. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. R. Duska, M. R. Hamblin, J. L. Miller, and T. Hasan Combination Photoimmunotherapy and Cisplatin: Effects on Human Ovarian Cancer Ex Vivo J Natl Cancer Inst, September 15, 1999; 91(18): 1557 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. A. Stewart, D. Mays, and J. A. Pietenpol Defective G1-S Cell Cycle Checkpoint Function Sensitizes Cells to Microtubule Inhibitor-induced Apoptosis Cancer Res., August 1, 1999; 59(15): 3831 - 3837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rowley and J. Zhang Caffeine-Mediated Override of Checkpoint Controls: A Requirement for rhp6 (Schizosaccharomyces pombe) Genetics, May 1, 1999; 152(1): 61 - 71. [Abstract] [Full Text]
|
|
|
|
|
|
B. J. Maurer, M. A. Ihnat, C. Morgan, J. Pullman, C. O'Brien, S. W. Johnson, J. S. Rasey, and M. M. Cornwell Growth of Human Tumor Cells in Macroporous Microcarriers Results in p53-Independent, Decreased Cisplatin Sensitivity Relative to Monolayers Mol. Pharmacol., May 1, 1999; 55(5): 938 - 947. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Nozaki, M. Tada, H. Kobayashi, C.-L. Zhang, Y. Sawamura, H. Abe, N. Ishii, and E. G. Van Meir Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression Neuro-oncol, April 1, 1999; 1(2): 124 - 137. [Abstract] [PDF]
|
|
|
|
|
|
F. Vikhanskaya, G. Colella, M. Valenti, S. Parodi, M. D'Incalci, and M. Broggini Cooperation between p53 and hMLH1 in a Human Colocarcinoma Cell Line in Response to DNA Damage Clin. Cancer Res., April 1, 1999; 5(4): 937 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Hagopian, G. B. Mills, A. R. Khokhar, R. C. Bast Jr., and Z. H. Siddik Expression of p53 in Cisplatin-resistant Ovarian Cancer Cell Lines: Modulation with the Novel Platinum Analogue (1R, 2R-Diaminocyclohexane)(trans-diacetato)(dichloro)-platinum(IV) Clin. Cancer Res., March 1, 1999; 5(3): 655 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, C Norbury, A. Harris, and T Toda Caffeine can override the S-M checkpoint in fission yeast J. Cell Sci., January 3, 1999; 112(6): 927 - 937. [Abstract] [PDF]
|
|
|
|
|
|
A. M. R. Fisher, A. Ferrario, N. Rucker, S. Zhang, and C. J. Gomer Photodynamic Therapy Sensitivity Is Not Altered in Human Tumor Cells after Abrogation of p53 Function Cancer Res., January 1, 1999; 59(2): 331 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yu, L. Orlandi, P. Wang, M. S. Orr, A. M. Senderowicz, E. A. Sausville, R. Silvestrini, N. Watanabe, H. Piwnica-Worms, and P. M. O'Connor UCN-01 Abrogates G2 Arrest through a Cdc2-dependent Pathway That Is Associated with Inactivation of the Wee1Hu Kinase and Activation of the Cdc25C Phosphatase J. Biol. Chem., December 11, 1998; 273(50): 33455 - 33464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bunz, A. Dutriaux, C. Lengauer, T. Waldman, S. Zhou, J. P. Brown, J. M. Sedivy, K. W. Kinzler, and B. Vogelstein Requirement for p53 and p21 to Sustain G2 Arrest After DNA Damage Science, November 20, 1998; 282(5393): 1497 - 1501. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S.-H. Liang, D. Hong, and M. F. Clarke Cooperation of a Single Lysine Mutation and a C-terminal Domain in the Cytoplasmic Sequestration of the p53 Protein J. Biol. Chem., July 31, 1998; 273(31): 19817 - 19821. [Abstract] |
