Cell Growth & Differentiation, Vol 4, Issue 9 761-768, Copyright © 1993 by American Association of Cancer Research

ARTICLES

Chimeras of herpes simplex viral VP16 and jun are oncogenic

ER Schuur, EJ Parker and PK Vogt
Department of Microbiology, University of Southern California School of Medicine, Los Angeles.

The Jun protein binds DNA and regulates transcription as a component of the AP-1 transcription factor complex. In its oncogenic form, Jun can transform cells in culture and cause tumors in animals. Both trans-activation and transformation require several functional domains of Jun, including an amino-terminal trans-activation domain. In this study, properties of Jun required for trans-activation and transformation were explored by replacing the trans-activation domains of c-Jun and its oncogenic counterpart, v-Jun, with the constitutively active trans-activation domain from the herpes simplex virus VP16 protein. The VP16-v-Jun chimera retained similar oncogenic properties to its parent, v-Jun. The VP16-c-Jun chimera, however, was considerably more oncogenic than c-Jun. Substitutions of a phenylalanine in the VP16 domain of the VP16-c-Jun chimera diminished or abolished transformation. Each of the chimeras bound to the AP-1 consensus recognition sequence from the collagenase promoter or from the human T-cell leukemia virus type I long terminal repeat in vitro. None of the VP16-Jun chimeras efficiently stimulated transcription from the collagenase promoter or an artificial promoter containing the human T-cell leukemia virus type I element in vivo. These results demonstrate that the Jun trans-activation domain can be replaced by a heterologous trans-activation domain with retention of oncogenic activity. However, this oncogenic activity is not reflected in the trans-activating properties of the chimeras.

This article has been cited by other articles:

				S.-l. Fu, I. Bottoli, M. Goller, and P. K. Vogt Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation PNAS, May 11, 1999; 96(10): 5716 - 5721. [Abstract] [Full Text] [PDF]

				S. Huguier, J. Baguet, S. Perez, H. van Dam, and M. Castellazzi Transcription Factor ATF2 Cooperates with v-Jun To Promote Growth Factor-Independent Proliferation In Vitro and Tumor Formation In Vivo Mol. Cell. Biol., December 1, 1998; 18(12): 7020 - 7029. [Abstract] [Full Text]

				U. Kruse, J. S. Iacovoni, M. E. Goller, and P. K. Vogt Hormone-regulatable neoplastic transformation induced by a Jun-estrogen receptor chimera PNAS, November 11, 1997; 94(23): 12396 - 12400. [Abstract] [Full Text] [PDF]