Enhanced apoptosis of B and T lymphocytes in TAFII105 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(II)s). Some TAF(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(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(II)105 and its mechanism of action in vivo by expressing two forms of dominant-negative mutant TAF(II)105 in mice. We show that TAF(II)105 has a pro-survival role in B and T lymphocytes, where the native protein is expressed. In addition, TAF(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.
Silkov
Antonina
A
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Wolstein
Orit
O
Shachar
Idit
I
Dikstein
Rivka
R
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology*; D035381:TATA-Binding Protein Associated Factors; D051996:Transcription Factor RelA; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D035381:TATA-Binding Protein Associated Factors; C491103:Taf4b protein, mouse; D051996:Transcription Factor RelA; D035362:Transcription Factor TFIID; D014157:Transcription Factors