1. ¹Chugai Research Institute for Molecular Medicine, 153-2 Nagai, Niihari-Mura, Ibaraki 300-41, Japan
2. ²National Institute of Bioscience and Human-Techno logy, AIST, 1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan

Correspondence: Renu Wadhwa, Chugai Research Institute for Molecular Medicine, 153-2 Nagai, Niihari-Mure,Ibaraki 300-41, Japan Tel: +81 298 30 6211; Fax +81 298 30 6270. E-mail: renu@cimmed.com

Received 30 October 1999; Revised 0  0000; Accepted 5 November 1999.

Abstract

In previous studies we have reported that a high level of expression of mot-2 protein results in malignant transformation of NIH 3T3 cells as analyzed by anchorage independent growth and nude mice assays [Kaul et al., Oncogene, 17, 907-11, 1998]. Mot-2 was found to interact with tumor suppressor protein p53. The transient overexpression of mot-2 was inhibitory to transcriptional activation function of p53 [Wadhwa et al., J. Biol. Chem., 273, 29586-91, 1998]. We demonstrate here that mot-2 transfected stable clone of NIH 3T3 that showed malignant properties indeed show inactivation of p53 function as assayed by exogenous p53 dependent reporter. The expression level of p53 in response to UV-irradiation was lower in NIH 3T3/mot-2 as compared to NIH 3T3 cells and also exhibited delay in reaching peak. Furthermore, upon serum starvation p53 was seen to translocate to the nucleus in NIH 3T3, but not in its mot-2 derivative. The data suggests that mot-2 mediated cytoplasmic sequestration and inactivation of p53 may operate, at least in part, for malignant phenotype of NIH 3T3/mot-2 cells.