TAF(II)105 is a sub-stoichiometric subunit of TFIID important for activation of anti-apoptotic genes and B cell specific genes by the transcription factors NF-kappaB and OCA-B. This subunit is highly enriched in B and T lymphocytes, and its expression is regulated at a posttranscriptional level. In the present study we investigated the subcellular localization of TAF(II)105. In normal B cells, a significant portion of native TAF(II)105 protein is found in the cytoplasm. Treatment of these cells with B cell-specific stimuli decreased the level of cytoplasmic TAF(II)105. In adherent cultured cells, TAF(II)105 is predominantly nuclear; however, a small fraction of the cells showed either cytoplasmic or homogenous distribution of TAF(II)105. Analysis of different TAF(II)105 mutants and green fluorescence protein fusion proteins identified a region composed of two adjacent sequences displaying nuclear export activity, suggesting that nuclear export of TAF(II)105 is mediated by a composite nuclear export signal. TAF(II)105 nuclear export signal is leptomycin B-resistant indicating that it belongs to a CRM1-independent nuclear export pathway. These results reveal a novel mode of regulation of a specialized component of the general transcription apparatus that may affect the transcription of its target genes.