This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Michieli, P. Articles by Givol, D. Search for Related Content PubMed PubMed Citation Articles by Michieli, P. Articles by Givol, D.

Induction of WAF1/CIP1 by a p53-independent Pathway¹

Laboratory of Cellular and Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [P. M., M. C., J. H. P., D. G.], and Department of Microbiology and Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [D. L., W. E. M.]

The p53-inducible gene WAF1/CIP1 encodes a M_r 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G₁ arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 "knock-out" mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by -irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed.

¹ Supported by a grant from the Italian Association for Cancer Research (to P. M.). D. G. is on leave from the Weizmann Institute of Science and acknowledges an award from the International Union Against Cancer. This work was also supported in part by grants CA55541 and CA54140 (to D. L. and W. E. M.).

² To whom requests for reprints should be addressed, at Laboratory of Cellular and Molecular Biology, National Cancer Institute, NIH, Building 37, Room 1E24, Bethesda, MD 20892. FAX: (301)496-8479. Phone: (301)496-1347.

Received 4/28/94. Accepted 5/19/94.

This article has been cited by other articles:

				V. S. Hawthorne, W.-C. Huang, C. L. Neal, L.-M. Tseng, M.-C. Hung, and D. Yu ErbB2-Mediated Src and Signal Transducer and Activator of Transcription 3 Activation Leads to Transcriptional Up-Regulation of p21Cip1 and Chemoresistance in Breast Cancer Cells Mol. Cancer Res., April 1, 2009; 7(4): 592 - 600. [Abstract] [Full Text] [PDF]

				M. YOSHIDA, Y. MATSUI, A. IIZUKA, and Y. IKARASHI G2-Phase Arrest Through p21(WAF1 / Cip1) Induction and cdc2 Repression by Gnidimacrin in Human Hepatoma HLE Cells Anticancer Res, April 1, 2009; 29(4): 1349 - 1354. [Abstract] [Full Text] [PDF]

				T. W. Young, D. G. Rosen, F. C. Mei, N. Li, J. Liu, X.-F. Wang, and X. Cheng Up-regulation of Tumor Susceptibility Gene 101 Conveys Poor Prognosis through Suppression of p21 Expression in Ovarian Cancer Clin. Cancer Res., July 1, 2007; 13(13): 3848 - 3854. [Abstract] [Full Text] [PDF]

				E. K.-P. Kong, W.-P. Chong, W. H.-S. Wong, C.-S. Lau, T.-M. Chan, P. K.-M. Ng, Y.-Q. Song, W. Mak, and Y.-L. Lau p21 gene polymorphisms in systemic lupus erythematosus Rheumatology, February 1, 2007; 46(2): 220 - 226. [Abstract] [Full Text] [PDF]

				S. Ouellet, F. Vigneault, M. Lessard, S. Leclerc, R. Drouin, and S. L. Guerin Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells Nucleic Acids Res., December 2, 2006; 34(22): 6472 - 6487. [Abstract] [Full Text] [PDF]

				M. Kaur, R. P. Singh, M. Gu, R. Agarwal, and C. Agarwal Grape Seed Extract Inhibits In vitro and In vivo Growth of Human Colorectal Carcinoma Cells. Clin. Cancer Res., October 15, 2006; 12(20): 6194 - 6202. [Abstract] [Full Text] [PDF]

				T. B. El-Abaseri, S. Putta, and L. A. Hansen Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor Carcinogenesis, February 1, 2006; 27(2): 225 - 231. [Abstract] [Full Text] [PDF]

				M. Law, E. Forrester, A. Chytil, P. Corsino, G. Green, B. Davis, T. Rowe, and B. Law Rapamycin Disrupts Cyclin/Cyclin-Dependent Kinase/p21/Proliferating Cell Nuclear Antigen Complexes and Cyclin D1 Reverses Rapamycin Action by Stabilizing These Complexes Cancer Res., January 15, 2006; 66(2): 1070 - 1080. [Abstract] [Full Text] [PDF]

				D. S. Kalinowski and D. R. Richardson The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer Pharmacol. Rev., December 1, 2005; 57(4): 547 - 583. [Abstract] [Full Text] [PDF]

				Y.-G. Goan, H.-K. Hsu, H.-C. Chang, Y.-P. Chou, K.-H. Chiang, and J.-T. Cheng Deregulated P21WAF1 Overexpression Impacts Survival of Surgically Resected Esophageal Squamous Cell Carcinoma Patients Ann. Thorac. Surg., September 1, 2005; 80(3): 1007 - 1016. [Abstract] [Full Text] [PDF]

				N. Nuntharatanapong, K. Chen, P. Sinhaseni, and J. F. Keaney Jr. EGF receptor-dependent JNK activation is involved in arsenite-induced p21Cip1/Waf1 upregulation and endothelial apoptosis Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H99 - H107. [Abstract] [Full Text] [PDF]

				M. Plataki, A. V. Koutsopoulos, K. Darivianaki, G. Delides, N. M. Siafakas, and D. Bouros Expression of Apoptotic and Antiapoptotic Markers in Epithelial Cells in Idiopathic Pulmonary Fibrosis Chest, January 1, 2005; 127(1): 266 - 274. [Abstract] [Full Text] [PDF]

				S.-i. Kurata, T. Okuyama, M. Osada, T. Watanabe, Y. Tomimori, S. Sato, A. Iwai, T. Tsuji, Y. Ikawa, and I. Katoh p51/p63 Controls Subunit {alpha}3 of the Major Epidermis Integrin Anchoring the Stem Cells to the Niche J. Biol. Chem., November 26, 2004; 279(48): 50069 - 50077. [Abstract] [Full Text] [PDF]

				J. Bai, H. Nakamura, S. Ueda, Y.-W. Kwon, T. Tanaka, S. Ban, and J. Yodoi Proteasome-dependent Degradation of Cyclin D1 in 1-Methyl-4-phenylpyridinium Ion (MPP+)-induced Cell Cycle Arrest J. Biol. Chem., September 10, 2004; 279(37): 38710 - 38714. [Abstract] [Full Text] [PDF]

				H. Vaghefi, A. L. Hughes, and K. E. Neet Nerve Growth Factor Withdrawal-mediated Apoptosis in Naive and Differentiated PC12 Cells through p53/Caspase-3-dependent and -independent Pathways J. Biol. Chem., April 9, 2004; 279(15): 15604 - 15614. [Abstract] [Full Text] [PDF]

				S. F. Shariat, H. Tokunaga, J. Zhou, J. Kim, G. E. Ayala, W. F. Benedict, and S. P. Lerner p53, p21, pRB, and p16 Expression Predict Clinical Outcome in Cystectomy With Bladder Cancer J. Clin. Oncol., March 15, 2004; 22(6): 1014 - 1024. [Abstract] [Full Text] [PDF]

				M. Nakaji, Y. Yano, T. Ninomiya, Y. Seo, K. Hamano, S. Yoon, M. Kasuga, T. Teramoto, Y. Hayashi, and H. Yokozaki IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat Carcinogenesis, March 1, 2004; 25(3): 389 - 397. [Abstract] [Full Text] [PDF]

				J. Yu, X.-W. Liu, and H.-R. C. Kim Platelet-derived Growth Factor (PDGF) Receptor-{alpha}-activated c-Jun NH2-terminal Kinase-1 Is Critical for PDGF-induced p21WAF1/CIP1 Promoter Activity Independent of p53 J. Biol. Chem., December 5, 2003; 278(49): 49582 - 49588. [Abstract] [Full Text] [PDF]

				K. Kameyama, C.-l. Huang, D. Liu, D. Masuya, T. Nakashima, S. Sumitomo, Y. Takami, M. Kinoshita, and H. Yokomise Reduced ING1b Gene Expression Plays an Important Role in Carcinogenesis of Non-Small Cell Lung Cancer Patients Clin. Cancer Res., October 15, 2003; 9(13): 4926 - 4934. [Abstract] [Full Text] [PDF]

				J. Plisiecka-Halasa, G. Karpinska, T. Szymanska, I. Ziolkowska, R. Madry, A. Timorek, J. Debniak, M. Ulanska, M. Jedryka, A. Chudecka-Glaz, et al. P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens Ann. Onc., July 1, 2003; 14(7): 1078 - 1085. [Abstract] [Full Text] [PDF]

				J. Gong, S. Ammanamanchi, T. C. Ko, and M. G. Brattain Transforming Growth Factor {beta}1 Increases the Stability of p21/WAF1/CIP1 Protein and Inhibits CDK2 Kinase Activity in Human Colon Carcinoma FET Cells Cancer Res., June 15, 2003; 63(12): 3340 - 3346. [Abstract] [Full Text] [PDF]

				M J Pellikainen, T T Pekola, K M Ropponen, V V Kataja, J K Kellokoski, M J Eskelinen, and V-M Kosma p21WAF1 expression in invasive breast cancer and its association with p53, AP-2, cell proliferation, and prognosis J. Clin. Pathol., March 1, 2003; 56(3): 214 - 220. [Abstract] [Full Text] [PDF]

				M. Frederich, M. Bentires-Alj, M. Tits, L. Angenot, R. Greimers, J. Gielen, V. Bours, and M.-P. Merville Isostrychnopentamine, an Indolomonoterpenic Alkaloid from Strychnos usambarensis, Induces Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1103 - 1110. [Abstract] [Full Text] [PDF]

				S. L. Rose, M. J. Goodheart, B. R. DeYoung, B. J. Smith, and R. E. Buller p21 Expression Predicts Outcome in p53-null Ovarian Carcinoma Clin. Cancer Res., March 1, 2003; 9(3): 1028 - 1032. [Abstract] [Full Text] [PDF]

				Y.-H. Ling, L. Liebes, J.-D. Jiang, J. F. Holland, P. J. Elliott, J. Adams, F. M. Muggia, and R. Perez-Soler Mechanisms of Proteasome Inhibitor PS-341-induced G2-M-Phase Arrest and Apoptosis in Human Non-Small Cell Lung Cancer Cell Lines Clin. Cancer Res., March 1, 2003; 9(3): 1145 - 1154. [Abstract] [Full Text] [PDF]

				W. C. Weinberg and M. F. Denning P21WAF1 CONTROL OF EPITHELIAL CELL CYCLE AND CELL FATE Critical Reviews in Oral Biology & Medicine, November 1, 2002; 13(6): 453 - 464. [Abstract] [Full Text] [PDF]

				S R McBride, N Leonard, and N J Reynolds Loss of p21WAF1 compartmentalisation in sebaceous carcinoma compared with sebaceous hyperplasia and sebaceous adenoma J. Clin. Pathol., October 1, 2002; 55(10): 763 - 766. [Abstract] [Full Text] [PDF]

				Q. Wu, P. Kirschmeier, T. Hockenberry, T.-Y. Yang, D. L. Brassard, L. Wang, T. McClanahan, S. Black, G. Rizzi, M. L. Musco, et al. Transcriptional Regulation during p21WAF1/CIP1-induced Apoptosis in Human Ovarian Cancer Cells J. Biol. Chem., September 20, 2002; 277(39): 36329 - 36337. [Abstract] [Full Text] [PDF]

				T. Shoji, F. Tanaka, T. Takata, K. Yanagihara, Y. Otake, N. Hanaoka, R. Miyahara, T. Nakagawa, Y. Kawano, S. Ishikawa, et al. Clinical Significance of p21 Expression in Non-Small-Cell Lung Cancer J. Clin. Oncol., September 15, 2002; 20(18): 3865 - 3871. [Abstract] [Full Text] [PDF]

				X. Tang, T. Yano, Y. Osuga, H. Matsumi, N. Yano, J. Xu, O. Wada, K. Koga, K. Kugu, O. Tsutsumi, et al. Cellular Mechanisms of Growth Inhibition of Human Epithelial Ovarian Cancer Cell Line by LH-Releasing Hormone Antagonist Cetrorelix J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3721 - 3727. [Abstract] [Full Text] [PDF]

				S. E. Boley, V. A. Wong, J. E. French, and L. Recio p53 Heterozygosity Alters the mRNA Expression of p53 Target Genes in the Bone Marrow in Response to Inhaled Benzene Toxicol. Sci., April 1, 2002; 66(2): 209 - 215. [Abstract] [Full Text] [PDF]

				A Baldi, A M Groeger, V Esposito, R Cassandro, G Tonini, T Battista, M P Di Marino, B Vincenzi, M Santini, A Angelini, et al. Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival Thorax, April 1, 2002; 57(4): 353 - 356. [Abstract] [Full Text] [PDF]

				Y. Li, D. Dowbenko, and L. A. Lasky AKT/PKB Phosphorylation of p21Cip/WAF1 Enhances Protein Stability of p21Cip/WAF1 and Promotes Cell Survival J. Biol. Chem., March 22, 2002; 277(13): 11352 - 11361. [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]

				V. Patel, T. Lahusen, T. Sy, E. A. Sausville, J. S. Gutkind, and A. M. Senderowicz Perifosine, a Novel Alkylphospholipid, Induces p21WAF1 Expression in Squamous Carcinoma Cells through a p53-independent Pathway, Leading to Loss in Cyclin-dependent Kinase Activity and Cell Cycle Arrest Cancer Res., March 1, 2002; 62(5): 1401 - 1409. [Abstract] [Full Text] [PDF]

				K. Fizazi, L. A. Martinez, C. R. Sikes, D. A. Johnston, L. C. Stephens, T. J. McDonnell, C. J. Logothetis, J. Trapman, L. L. Pisters, N. G. Ordonez, et al. The Association of p21(WAF-1/CIP1) with Progression to Androgen-independent Prostate Cancer Clin. Cancer Res., March 1, 2002; 8(3): 775 - 781. [Abstract] [Full Text] [PDF]

				Q. Zhu, J.-W. Zhang, H.-Q. Zhu, Y.-L. Shen, M. Flexor, P.-M. Jia, Y. Yu, X. Cai, S. Waxman, M. Lanotte, et al. Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk Blood, February 1, 2002; 99(3): 1014 - 1022. [Abstract] [Full Text] [PDF]

				M. Schmidt, Y. Lu, J. M. Parant, G. Lozano, G. Bacher, T. Beckers, and Z. Fan Differential Roles of p21Waf1 and p27Kip1 in Modulating Chemosensitivity and Their Possible Application in Drug Discovery Studies Mol. Pharmacol., November 1, 2001; 60(5): 900 - 906. [Abstract] [Full Text] [PDF]

				H. J. Kwun, E. Y. Jung, J. Y. Ahn, M. N. Lee, and K. L. Jang p53-dependent transcriptional repression of p21waf1 by hepatitis C virus NS3 J. Gen. Virol., September 1, 2001; 82(9): 2235 - 2241. [Abstract] [Full Text] [PDF]

				J. Martin-Caballero, J. M. Flores, P. Garcia-Palencia, and M. Serrano Tumor Susceptibility of p21Waf1/Cip1-deficient Mice Cancer Res., August 1, 2001; 61(16): 6234 - 6238. [Abstract] [Full Text] [PDF]

				J. Gao and D. R. Richardson The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents, IV: the mechanisms involved in inhibiting cell-cycle progression Blood, August 1, 2001; 98(3): 842 - 850. [Abstract] [Full Text] [PDF]

				S. Wakino, U. Kintscher, S. Kim, S. Jackson, F. Yin, S. Nagpal, R. A. S. Chandraratna, W. A. Hsueh, and R. E. Law Retinoids Inhibit Proliferation of Human Coronary Smooth Muscle Cells by Modulating Cell Cycle Regulators Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 746 - 751. [Abstract] [Full Text] [PDF]

				T. MIYAJI, A. KATO, H. YASUDA, Y. FUJIGAKI, and A. HISHIDA Role of the Increase in p21 in Cisplatin-Induced Acute Renal Failure in Rats J. Am. Soc. Nephrol., May 1, 2001; 12(5): 900 - 908. [Abstract] [Full Text]

				Y. Moriyama, S. Nishiguchi, A. Tamori, N. Koh, Y. Yano, S. Kubo, K. Hirohashi, and S. Otani Tumor-Suppressor Effect of Interferon Regulatory Factor-1 in Human Hepatocellular Carcinoma Clin. Cancer Res., May 1, 2001; 7(5): 1293 - 1298. [Abstract] [Full Text]

				S. G. Moréno, B. Dutrillaux, and H. Coffigny Status of p53, p21, mdm2, pRb Proteins, and DNA Methylation in Gonocytes of Control and {{gamma}}-Irradiated Rats During Testicular Development Biol Reprod, May 1, 2001; 64(5): 1422 - 1431. [Abstract] [Full Text]

				W. C. Yang, J. Mathew, A. Velcich, W. Edelmann, R. Kucherlapati, M. Lipkin, K. Yang, and L. H. Augenlicht Targeted Inactivation of the p21WAF1/cip1 Gene Enhances Apc-initiated Tumor Formation and the Tumor-promoting Activity of a Western-Style High-Risk Diet by Altering Cell Maturation in the Intestinal Mucosa Cancer Res., January 1, 2001; 61(2): 565 - 569. [Abstract] [Full Text]

				A.-C. Hellin, M. Bentires-Alj, M. Verlaet, V. Benoit, J. Gielen, V. Bours, and M.-P. Merville Roles of Nuclear Factor-kappa B, p53, and p21/WAF1 in Daunomycin-Induced Cell Cycle Arrest and Apoptosis J. Pharmacol. Exp. Ther., December 1, 2000; 295(3): 870 - 878. [Abstract] [Full Text]

				F. Mouriaux, C.-A. Maurage, P. Labalette, B. Sablonnière, F. Malecaze, and J.-M. Darbon Cyclin-Dependent Kinase Inhibitory Protein Expression in Human Choroidal Melanoma Tumors Invest. Ophthalmol. Vis. Sci., September 1, 2000; 41(10): 2837 - 2843. [Abstract] [Full Text]

				S. LANG, A. HARTNER, R. B. STERZEL, and H. O. SCHÖCKLMANN Requirement of Cyclin D1 in Mesangial Cell Mitogenesis J. Am. Soc. Nephrol., August 1, 2000; 11(8): 1398 - 1408. [Abstract] [Full Text]

				J. Sjöström, C. Blomqvist, P. Heikkilä, K. von Boguslawski, A. Räisänen-Sokolowski, N.-O. Bengtsson, I. Mjaaland, P. Malmström, B. Ostenstadt, J. Bergh, et al. Predictive Value of p53, mdm-2, p21, and mib-1 for Chemotherapy Response in Advanced Breast Cancer Clin. Cancer Res., August 1, 2000; 6(8): 3103 - 3110. [Abstract] [Full Text]

				M. Migaldi, A. Sgambato, L. Garagnani, R. Ardito, P. Ferrari, Carmela De Gaetani, A. Cittadini, and G. P. Trentini Loss of p21Waf1 Expression Is a Strong Predictor of Reduced Survival in Primary Superficial Bladder Cancers Clin. Cancer Res., August 1, 2000; 6(8): 3131 - 3138. [Abstract] [Full Text]

				A. Besson and V. W. Yong Involvement of p21Waf1/Cip1 in Protein Kinase C Alpha-Induced Cell Cycle Progression Mol. Cell. Biol., July 1, 2000; 20(13): 4580 - 4590. [Abstract] [Full Text]

				Y. Nakanishi, X.-H. Pei, K. Takayama, F. Bai, M. Izumi, K. Kimotsuki, K. Inoue, T. Minami, H. Wataya, and N. Hara Polycyclic Aromatic Hydrocarbon Carcinogens Increase Ubiquitination of p21 Protein after the Stabilization of p53 and the Expression of p21 Am. J. Respir. Cell Mol. Biol., June 1, 2000; 22(6): 747 - 754. [Abstract] [Full Text]

				W. H. Park, J. G. Seol, E. S. Kim, J. M. Hyun, C. W. Jung, C. C. Lee, B. K. Kim, and Y. Y. Lee Arsenic Trioxide-mediated Growth Inhibition in MC/CAR Myeloma Cells via Cell Cycle Arrest in Association with Induction of Cyclin-dependent Kinase Inhibitor, p21, and Apoptosis Cancer Res., June 1, 2000; 60(11): 3065 - 3071. [Abstract] [Full Text] [PDF]

				R. Ralhan, S. Agarwal, M. Mathur, B. Wasylyk, and A. Srivastava Association between Polymorphism in p21Waf1/Cip1 Cyclin-dependent Kinase Inhibitor Gene and Human Oral Cancer Clin. Cancer Res., June 1, 2000; 6(6): 2440 - 2447. [Abstract] [Full Text]

				R. Amson, J.-M. Lassalle, H. Halley, S. Prieur, F. Lethrosne, J.-P. Roperch, D. Israeli, M.-C. Gendron, C. Duyckaerts, F. Checler, et al. Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice PNAS, May 9, 2000; 97(10): 5346 - 5350. [Abstract] [Full Text] [PDF]

				M. Burchardt, T. Burchardt, A. Shabsigh, A. De La Taille, M. C. Benson, and I. Sawczuk Current Concepts in Biomarker Technology for Bladder Cancers Clin. Chem., May 1, 2000; 46(5): 595 - 605. [Abstract] [Full Text] [PDF]

				R. H. Weiss, A. Joo, and C. Randour p21Waf1/Cip1 Is an Assembly Factor Required for Platelet-derived Growth Factor-induced Vascular Smooth Muscle Cell Proliferation J. Biol. Chem., March 31, 2000; 275(14): 10285 - 10290. [Abstract] [Full Text] [PDF]

				S. M. Mendrysa and M. E. Perry The p53 Tumor Suppressor Protein Does Not Regulate Expression of Its Own Inhibitor, MDM2, Except under Conditions of Stress Mol. Cell. Biol., March 15, 2000; 20(6): 2023 - 2030. [Abstract] [Full Text]

				C. R. Antonescu, D. H. Leung, M. Dudas, M. Ladanyi, M. Brennan, J. M. Woodruff, and C. Cordon-Cardo Alterations of Cell Cycle Regulators in Localized Synovial Sarcoma : A Multifactorial Study with Prognostic Implications Am. J. Pathol., March 1, 2000; 156(3): 977 - 983. [Abstract] [Full Text] [PDF]

				W. Wang, H. Furneaux, H. Cheng, M. C. Caldwell, D. Hutter, Y. Liu, N. Holbrook, and M. Gorospe HuR Regulates p21 mRNA Stabilization by UV Light Mol. Cell. Biol., February 1, 2000; 20(3): 760 - 769. [Abstract] [Full Text]

				Y. Shirakawa, Y. Naomoto, M. Kimura, R. Kawashima, T. Yamatsuji, T. Tamaki, M. Hamada, M. Haisa, and N. Tanaka Topological Analysis of p21WAF1/CIP1 Expression in Esophageal Squamous Dysplasia Clin. Cancer Res., February 1, 2000; 6(2): 541 - 550. [Abstract] [Full Text]

				F. Vikhanskaya, M. D'Incalci, and M. Broggini p73 competes with p53 and attenuates its response in a human ovarian cancer cell line Nucleic Acids Res., January 15, 2000; 28(2): 513 - 519. [Abstract] [Full Text] [PDF]

				H. Xiao, T. Hasegawa, and K.-i. Isobe p300 Collaborates with Sp1 and Sp3 in p21waf1/cip1 Promoter Activation Induced by Histone Deacetylase Inhibitor J. Biol. Chem., January 14, 2000; 275(2): 1371 - 1376. [Abstract] [Full Text] [PDF]

				J.-Y. Shin, H.-S. Kim, J. Park, J.-B. Park, and J.-Y. Lee Mechanism for Inactivation of the KIP Family Cyclin-dependent Kinase Inhibitor Genes in Gastric Cancer Cells Cancer Res., January 1, 2000; 60(2): 262 - 265. [Abstract] [Full Text]

				H. P. Kourea, C. Cordon-Cardo, M. Dudas, D. Leung, and J. M. Woodruff Expression of p27kip and Other Cell Cycle Regulators in Malignant Peripheral Nerve Sheath Tumors and Neurofibromas : The Emerging Role of p27kip in MalignantTransformation of Neurofibromas Am. J. Pathol., December 1, 1999; 155(6): 1885 - 1891. [Abstract] [Full Text] [PDF]

				C. Pfister, L. Moore, P. Allard, H. Larue, L. Lacombe, B. Tetu, F. Meyer, and Y. Fradet Predictive Value of Cell Cycle Markers p53, MDM2, p21, and Ki-67 in Superficial Bladder Tumor Recurrence Clin. Cancer Res., December 1, 1999; 5(12): 4079 - 4084. [Abstract] [Full Text] [PDF]

				D. Kardassis, P. Papakosta, K. Pardali, and A. Moustakas c-Jun Transactivates the Promoter of the Human p21WAF1/Cip1 Gene by Acting as a Superactivator of the Ubiquitous Transcription Factor Sp1 J. Biol. Chem., October 8, 1999; 274(41): 29572 - 29581. [Abstract] [Full Text] [PDF]

				G. Pruneri, L. Pignataro, N. Carboni, R. Buffa, D. Di Finizio, B. M. Cesana, and A. Neri Clinical Relevance of Expression of the CIP/KIP Cell-Cycle Inhibitors p21 and p27 in Laryngeal Cancer J. Clin. Oncol., October 1, 1999; 17(10): 3150 - 3159. [Abstract] [Full Text] [PDF]

				S. El Mansouri, A. Martin, A. Mercadier, C. Capoulade, V. Maréchal, J. Wiels, J. Feuillard, and M. Raphaël High Expression of MDM2 Protein and Low Rate of p21WAF1/CIP1 Expression in SCID Mice Epstein Barr Virus-induced Lymphoproliferation J. Histochem. Cytochem., October 1, 1999; 47(10): 1315 - 1322. [Abstract] [Full Text]

				W. E. Hobbs II and N. A. DeLuca Perturbation of Cell Cycle Progression and Cellular Gene Expression as a Function of Herpes Simplex Virus ICP0 J. Virol., October 1, 1999; 73(10): 8245 - 8255. [Abstract] [Full Text] [PDF]

				M. Baekelandt, R. Holm, C. G. Trope, J. M. Nesland, and G. B. Kristensen Lack of Independent Prognostic Significance of p21 and p27 Expression in Advanced Ovarian Cancer: An Immunohistochemical Study Clin. Cancer Res., October 1, 1999; 5(10): 2848 - 2853. [Abstract] [Full Text] [PDF]

				G. I. Shapiro, D. A. Koestner, C. B. Matranga, and B. J. Rollins Flavopiridol Induces Cell Cycle Arrest and p53-independent Apoptosis in Non-Small Cell Lung Cancer Cell Lines Clin. Cancer Res., October 1, 1999; 5(10): 2925 - 2938. [Abstract] [Full Text] [PDF]

				L. Kivinen and M. Laiho Ras- and Mitogen-activated Protein Kinase Kinase-dependent and -independent Pathways in p21Cip1/Waf1 Induction by Fibroblast Growth Factor-2, Platelet-derived Growth Factor, and Transforming Growth Factor-{beta}1 Cell Growth Differ., September 1, 1999; 10(9): 621 - 628. [Abstract] [Full Text]

				C. E. Shin, R. A. Falcone Jr., C. J. Kemp, C. R. Erwin, D. A. Litvak, B. M. Evers, and B. W. Warner Intestinal adaptation and enterocyte apoptosis following small bowel resection is p53 independent Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G717 - G724. [Abstract] [Full Text] [PDF]

				Y.-P. Lu, Y.-R. Lou, P. Yen, D. Mitchell, M.-T. Huang, and A. H. Conney Time Course for Early Adaptive Responses to Ultraviolet B Light in the Epidermis of SKH-1 Mice Cancer Res., September 1, 1999; 59(18): 4591 - 4602. [Abstract] [Full Text] [PDF]

				S. Natsugoe, S. Nakashima, M. Matsumoto, C. Xiangming, H. Okumura, F. Kijima, S. Ishigami, Y. Takebayashi, M. Baba, S. Takao, et al. Expression of p21WAF1/Cip1 in the p53-dependent Pathway Is Related to Prognosis in Patients with Advanced Esophageal Carcinoma Clin. Cancer Res., September 1, 1999; 5(9): 2445 - 2449. [Abstract] [Full Text] [PDF]

				G. Darnell and D.R. Richardson The Potential of Iron Chelators of the Pyridoxal Isonicotinoyl Hydrazone Class as Effective Antiproliferative Agents III: The Effect of the Ligands on Molecular Targets Involved in Proliferation Blood, July 15, 1999; 94(2): 781 - 792. [Abstract] [Full Text] [PDF]

				M. Mutoh, F.-D. T. Lung, Y.-Q. Long, P. P. Roller, R. S. Sikorski, and P. M. O'Connor A p21Waf1/Cip1 Carboxyl-terminal Peptide Exhibited Cyclin-dependent Kinase-inhibitory Activity and Cytotoxicity When Introduced into Human Cells Cancer Res., July 1, 1999; 59(14): 3480 - 3488. [Abstract] [Full Text] [PDF]

				J. D. heng, B. A. Werness, J. S. Babb, and N. J. Meropol Paradoxical Correlations of Cyclin-dependent Kinase Inhibitors p21waf1/cip1 and p27kip1 in Metastatic Colorectal Carcinoma Clin. Cancer Res., May 1, 1999; 5(5): 1057 - 1062. [Abstract] [Full Text] [PDF]

				M. Shoji, Y. Dobashi, S. Morinaga, S.-X. Jiang, and T. Kameya Tumor Extension and Cell Proliferation in Adenocarcinomas of the Lung Am. J. Pathol., March 1, 1999; 154(3): 909 - 918. [Abstract] [Full Text] [PDF]

				J. U. Gutterman and D. Choubey Retardation of Cell Proliferation after Expression of p202 Accompanies an Increase in p21WAF1/CIP1 Cell Growth Differ., February 1, 1999; 10(2): 93 - 100. [Abstract] [Full Text]

				K. Sharma, Y. C. Patel, and C. B. Srikant C-Terminal Region of Human Somatostatin Receptor 5 Is Required for Induction of Rb and G1 Cell Cycle Arrest Mol. Endocrinol., January 1, 1999; 13(1): 82 - 90. [Abstract] [Full Text]

				G. Gentilini, N. E. Kirschbaum, J. A. Augustine, R. H. Aster, and G. P. Visentin Inhibition of Human Umbilical Vein Endothelial Cell Proliferation by the CXC Chemokine, Platelet Factor 4 (PF4), Is Associated With Impaired Downregulation of p21Cip1/WAF1 Blood, January 1, 1999; 93(1): 25 - 33. [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]

				A. Nalca and V. M. Rangnekar The G1-phase Growth-arresting Action of Interleukin-1 Is Independent of p53 and p21/WAF1 Function J. Biol. Chem., November 13, 1998; 273(46): 30517 - 30523. [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. M. Buchmann, S. Swaminathan, and B. Thimmapaya Regulation of Cellular Genes in a Chromosomal Context by the Retinoblastoma Tumor Suppressor Protein Mol. Cell. Biol., August 1, 1998; 18(8): 4565 - 4576. [Abstract] [Full Text]

				S E Coupland, N Bechrakis, A Schüler, I Anagnostopoulos, M Hummel, N Bornfeld, and H Stein Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma Br J Ophthalmol, August 1, 1998; 82(8): 961 - 970. [Abstract] [Full Text]

				G. Brooks, R. A Poolman, and J.-M. Li Arresting developments in the cardiac myocyte cell cycle: Role of cyclin-dependent kinase inhibitors Cardiovasc Res, August 1, 1998; 39(2): 301 - 311. [Abstract] [Full Text] [PDF]

				M. Tanikawa, K. Yamada, K. Tominaga, H. Morisaki, Y. Kaneko, K. Ikeda, M. Suzuki, T. Kiho, K. Tomokiyo, K. Furuta, et al. Potent Prostaglandin A1 Analogs That Suppress Tumor Cell Growth through Induction of p21 and Reduction of Cyclin E J. Biol. Chem., July 17, 1998; 273(29): 18522 - 18527. [Abstract] [Full Text] [PDF]

				S. Waga and B. Stillman Cyclin-Dependent Kinase Inhibitor p21 Modulates the DNA Primer-Template Recognition Complex Mol. Cell. Biol., July 1, 1998; 18(7): 4177 - 4187. [Abstract] [Full Text]

				C. Todd and N. J. Reynolds Up-Regulation of p21WAF1 by Phorbol Ester and Calcium in Human Keratinocytes through a Protein Kinase C-Dependent Pathway Am. J. Pathol., July 1, 1998; 153(1): 39 - 45. [Abstract] [Full Text] [PDF]

				R. A. Steinman, J. Huang, B. Yaroslavskiy, J. P. Goff, E. D. Ball, and A. Nguyen Regulation of p21(WAF1) Expression During Normal Myeloid Differentiation Blood, June 15, 1998; 91(12): 4531 - 4542. [Abstract] [Full Text] [PDF]

				E. Perz and J. G. Kuhn Review : p53 in the pathogenesis, diagnosis, and treatment of cancer Journal of Oncology Pharmacy Practice, June 1, 1998; 4(2): 75 - 102. [Abstract] [PDF]

				B. Tong, H. L. Grimes, T.-Y. Yang, S. E. Bear, Z. Qin, K. Du, W. S. El-Deiry, and P. N. Tsichlis The Gfi-1B Proto-Oncoprotein Represses p21WAF1 and Inhibits Myeloid Cell Differentiation Mol. Cell. Biol., May 1, 1998; 18(5): 2462 - 2473. [Abstract] [Full Text]

				M. Gorospe, X. Wang, and N. J. Holbrook p53-Dependent Elevation of p21Waf1 Expression by UV Light Is Mediated through mRNA Stabilization and Involves a Vanadate-Sensitive Regulatory System Mol. Cell. Biol., March 1, 1998; 18(3): 1400 - 1407. [Abstract] [Full Text]

				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]