This Article Full Text 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 Wadhwa, R. Articles by Kaul, S. C. Search for Related Content PubMed PubMed Citation Articles by Wadhwa, R. Articles by Kaul, S. C.

Selective Toxicity of MKT-077 to Cancer Cells Is Mediated by Its Binding to the hsp70 Family Protein mot-2 and Reactivation of p53 Function

Chugai Research Institute for Molecular Medicine, 153-2 Nagai, Niihari, Ibaraki 300-41, Japan [R. W., T. S., A. Y., H. N.]; Children’s Medical Research Institute, Sydney, New South Wales 2145, Australia [R. R. R.]; Ludwig Institute for Cancer Research, Melbourne, Victoria 3050, Australia [R. S., H. M.]; National Institute of Bioscience and Human-Technology, 1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan [S. C. K.]

MKT-077, a cationic rhodacyanine dye analogue has been under preclinical cancer therapeutical trials because of its selective toxicity to cancer cells. Its cellular targets and mechanism of action remain poorly understood. Here we report that MKT-077 binds to an hsp70 family member, mortalin (mot-2), and abrogates its interactions with the tumor suppressor protein, p53. In cancer cells, but not in normal cells, MKT-077 induced release of wild-type p53 from cytoplasmically sequestered p53-mot-2 complexes and rescued its transcriptional activation function. Thus, MKT-077 may be particularly useful for therapy of cancers with wild-type p53.

This article has been cited by other articles:

				C. Walker, S. A. Bottger, J. Mulkern, E. Jerszyk, M. Litvaitis, and M. Lesser Mass Culture and Characterization of Tumor Cells From a Naturally Occurring Invertebrate Cancer Model: Applications for Human and Animal Disease and Environmental Health Biol. Bull., February 1, 2009; 216(1): 23 - 39. [Abstract] [Full Text] [PDF]

				J. C. Ghosh, T. Dohi, B. H. Kang, and D. C. Altieri Hsp60 Regulation of Tumor Cell Apoptosis J. Biol. Chem., February 22, 2008; 283(8): 5188 - 5194. [Abstract] [Full Text] [PDF]

				S. Bottger, E. Jerszyk, B. Low, and C. Walker Genotoxic Stress-Induced Expression of p53 and Apoptosis in Leukemic Clam Hemocytes with Cytoplasmically Sequestered p53 Cancer Res., February 1, 2008; 68(3): 777 - 782. [Abstract] [Full Text] [PDF]

				N. Widodo, K. Kaur, B. G. Shrestha, Y. Takagi, T. Ishii, R. Wadhwa, and S. C. Kaul Selective Killing of Cancer Cells by Leaf Extract of Ashwagandha: Identification of a Tumor-Inhibitory Factor and the First Molecular Insights to Its Effect Clin. Cancer Res., April 1, 2007; 13(7): 2298 - 2306. [Abstract] [Full Text] [PDF]

				N. Widodo, C. C. Deocaris, K. Kaur, K. Hasan, T. Yaguchi, K. Yamasaki, T. Sugihara, T. Ishii, R. Wadhwa, and S. C. Kaul Stress Chaperones, Mortalin, and Pex19p Mediate 5-Aza-2' Deoxycytidine-Induced Senescence of Cancer Cells by DNA Methylation-Independent Pathway J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2007; 62(3): 246 - 255. [Abstract] [Full Text] [PDF]

				C. Walker, S. Bottger, and B. Low Mortalin-Based Cytoplasmic Sequestration of p53 in a Nonmammalian Cancer Model Am. J. Pathol., May 1, 2006; 168(5): 1526 - 1530. [Abstract] [Full Text] [PDF]

				S. C. Kaul, S. Aida, T. Yaguchi, K. Kaur, and R. Wadhwa Activation of Wild Type p53 Function by Its Mortalin-binding, Cytoplasmically Localizing Carboxyl Terminus Peptides J. Biol. Chem., November 25, 2005; 280(47): 39373 - 39379. [Abstract] [Full Text] [PDF]

				R. Wadhwa, L. Colgin, T. Yaguchi, K. Taira, R. R. Reddel, and S. C. Kaul Rhodacyanine Dye MKT-077 Inhibits in Vitro Telomerase Assay But Has No Detectable Effects on Telomerase Activity in Vivo Cancer Res., August 1, 2002; 62(15): 4434 - 4438. [Abstract] [Full Text] [PDF]

				J.-L. Mergny, J.-F. Riou, P. Mailliet, M.-P. Teulade-Fichou, and E. Gilson Natural and pharmacological regulation of telomerase Nucleic Acids Res., February 15, 2002; 30(4): 839 - 865. [Abstract] [Full Text] [PDF]