摘要
Transcription factor TFIIA is controlled by complex regulatory networks including proteolysis by the protease Taspase 1, though the full impact of cleavage remains elusive. Here, we demonstrate that in contrast to the general assumption, de novo produced TFIIA is rapidly confined to the cytoplasm via an evolutionary conserved nuclear export signal （NES, amino acids ^21VINDVRDIFL^30）, interacting with the nuclear export receptor Exportin-1/chromosomal region maintenance 1 （Crml）. Chemical export inhibition or genetic inactivation of the NES not only promotes TFIIA＇s nuclear localization but also affects its transcrip- tional activity. Notably, Taspase 1 processing promotes TFIIA＇s nuclear accumulation by NES masking, and modulates its tran- scriptional activity. Moreover, TFIIA complex formation with the TATA box binding protein （TBP） is cooperatively enhanced by inhibition of proteolysis and nuclear export, leading to an increase of the ceil cycle inhibitor p16INK, which is counteracted by pre- vention of TBP binding. We here identified a novel mechanism how proteolysis and nuclear transport cooperatively fine-tune tran- scriptional programs.
