A short domain within Bcl-3 is responsible for its lymphocyte survival activity.
The NFkappaB factor Bcl-3 influences the survival of T cells when they are activated to take part in immune responses. Because treatment of mice with adjuvant results in the increased expression of Bcl-3 in T cells, where it has survival-promoting effects, Bcl-3 may be an important, limiting factor that is supplied to T cells only when they are contributing to an appropriate immune response to infection, and not when spuriously activated by self-antigens. Although Bcl-3 is a member of the NFkappaB/Rel/IkappaB family of transcription factors, the means by which it promotes T cell survival is not obvious because Bcl-3 is unique in having an ankyrin repeat domain, like inhibitory IkappaB proteins, while also possessing domains capable of transcriptional activation, like Rel proteins. In order to understand the basis for the survival activity of Bcl-3, deletion mutants were engineered and tested in a retroviral gene transfer sytem. We report that most of Bcl-3 can be deleted without diminishing its ability to prolong the survival of activated T and B cells, and find that its lymphocyte survival domain maps to the vicinity of its first and second ankryin repeats. This information sets the stage for experiments in which a focused search can be made for mediators of Bcl-3 survival effects.
Mitchell
Thomas C
TC
Institute for Cellular Therapeutics, J. Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. tom.mitchell@louisville.edu
Thompson
Bruce S
BS
Trent
John O
JO
Casella
Carolin R
CR
D000818:Animals; D017089:Ankyrin Repeat; D000081242:B-Cell Lymphoma 3 Protein; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002470:Cell Survival; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression; D018014:Gene Transfer Techniques; D051379:Mice; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D014157:Transcription Factors
D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors