Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription

Takayoshi Shimohata , Toshihiro Nakajima , Mitsunori Yamada , Chiharu Uchida , Osamu Onodera , Satoshi Naruse , Tetsuya Kimura , Reiji Koide , Kenkichi Nozaki , Yasuteru Sano , Hiroshi Ishiguro , Kumi Sakoe , Takayuki Ooshima , Aki Sato , Takeshi Ikeuchi , Mutsuo Oyake , Toshiya Sato , Yasuyuki Aoyagi , Isao Hozumi , Toshiharu Nagatsu , Yoshihisa Takiyama , Masatoyo Nishizawa , Jun Goto , Ichiro Kanazawa , Irwin Davidson (1, 2) , Naoko Tanese , Hitoshi Takahashi , Shoji Tsuji

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

At least eight inherited neurodegenerative diseases are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches are implicated, the molecular mechanisms of neurodegeneration remain unclear. We found that expanded polyQ stretches preferentially bind to TAFII130, a coactivator involved in cAMP-responsive element binding protein (CREB)-dependent transcriptional activation, and strongly suppress CREB-dependent transcriptional activation. The suppression of CREB-dependent transcription and the cell death induced by polyQ stretches were restored by the co-expression of TAFII130. Our results indicate that interference of transcription by the binding of TAFII130 with expanded polyQ stretches is involved in the pathogenetic mechanisms underlying neurodegeneration.

Domaines: Biochimie, Biologie Moléculaire

Takayoshi Shimohata, Toshihiro Nakajima, Mitsunori Yamada, Chiharu Uchida, Osamu Onodera, et al.. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nature Genetics, 2000, 26 (1), pp.29-36. ⟨10.1038/79139⟩. ⟨hal-04093236⟩