A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1

作者：Nnamani Mauris C; Ganguly Soumya; Erkenbrack Eric M; Lynch Vincent J; Mizoue Laura S; Tong Yingchun; Darling Heather L; Fuxreiter Monika; Meiler Jens^*; Wagner Guenter P^*

来源：Cell Reports, 2016, 15(10): 2097-2108.

DOI：10.1016/j.celrep.2016.04.088

Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.

• 出版日期2016-6-7