Andrew Liss

Focus of Research:

Currently Attending:
Massachusetts General Hospital

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Mutational analysis of the v-Rel dimerization interface reveals a critical role for v-Rel homodimers in transformation

Co-Authors A.S. Liss and H.R. Bose, Jr.

The v-rel oncogene encoded by reticuloendotheliosis virus strain T is the acutely transforming member of the Rel/NF-{kappa}B family of transcription factors. In v-Rel-transformed cells, v-Rel exists as homodimers or heterodimers with the endogenous Rel/NF-{kappa}B proteins c-Rel, NF-{kappa}B1, NF-{kappa}B2, and RelA. To examine the contribution of these complexes to v-Rel-mediated transformation, mutations were introduced into the dimerization interface of v-Rel to generate v-Rel mutants with selective dimerization properties. Nine mutants are described in this study that are defective in homodimer and/or heterodimer formation with specific Rel/NF-{kappa}B family members. Viruses expressing mutants that failed to homodimerize but were able to form heterodimeric complexes were unable to transform splenic lymphocytes in vitro, indicating that the dimerization of v-Rel with endogenously expressed Rel/NF-{kappa}B proteins is not in itself sufficient for transformation. In addition, two partially transforming mutants were identified that exhibited an impaired ability to form homodimers. Sequence analysis of the proviral DNA from cells transformed by these mutants revealed the presence of multiple secondary mutations in sequences responsible for dimerization and DNA binding. Two of these mutations either enhanced or restored the ability of these proteins to bind DNA as a homodimer. Viruses expressing these proteins transformed cells at levels comparable to or slightly less than v-Rel, suggesting that a threshold level of DNA binding by v-Rel homodimers is required for transformation.

J Virol. 2002 May;76(10):4928-39.

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