Enhanced Apoptosis of B and T Lymphocytes in TAF sub(II)105 Dominant-negative Transgenic Mice Is Linked to Nuclear Factor- Kappa B

The general transcription factor TFIID is composed of the TATA-binding protein (TBP) and 12-14 TBP-associated factors (TAF sub(II)s). Some TAF sub(II)s act as bridges between transcription activators and the general transcription machinery through direct interaction with activation domains. Although TAF-mediated transcription activation has been established, there is little genetic evidence connecting it to binding of an activator. TAF sub(II)105 is a substoichiometric subunit of transcription factor IID highly expressed in B lymphocytes. In this study, we examined the physiological role of TAF sub(II)105 and its mechanism of action in vivo by expressing two forms of dominant-negative mutant TAF sub(II)105 in mice. We show that TAF sub(II)105 has a pro-survival role in B and T lymphocytes, where the native protein is expressed. In addition, TAF sub(II)105 is important for T cell maturation and for production of certain antibody isotypes. These phenotypic alterations were absent in mice expressing a dominant-negative mutant that lacks one of the domains mediating p65/RelA binding in vitro. These findings provide support to the notion that interaction between the activator and TAF is important for their function in vivo.