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Science 17 April 1992:
Vol. 256. no. 5055, pp. 367 - 370
DOI: 10.1126/science.256.5055.367
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Articles

Identification of a Naturally Occurring Transforming Variant of the p65 Subunit of NF-KB

Ramaswamy Narayanan 1, John F. Klement 2, Steven M. Ruben 2, Kimberly A. Higgins 1, and Craig A. Rosen 2

1 Department of Molecular Genetics, Hoffmann-La Roche, Inc., Nutley, NJ 07110
2 Department of Gene Regulation, Roche Institute of Molecular Biology, 340 Kingsland Street, Nutley, NJ 07110

Transcription factor NF-KB comprises two proteins, p50 and p65, that have sequence similarity to the v-rel oncogene. In primary hematopoietic cell populations an alternatively spliced form of NF-KB p65 mRNA was observed that encoded a protein designated p65Dgr. Expression of the p65Dgr cDNA in Rat-1 fibroblasts resulted in focus formation, anchorage- independent growth in soft agar, and tumor formation in athymic nude mice, effects not obtained with expression of p65 or a p65Dgr mutant that contains a disruption within the transcriptional activation domain. Thus, p65Dgr, which associated weakly and interfered with DNA binding by p65, may sequester an essential limiting regulatory factor or factors required for NF-KB function.


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