Role of LXXLL motif in modulation of estrogen receptor signaling and its potential application

Estrogen receptor(ER), one member of the nuclear receptor superfamily, via binding to estrogen, plays important roles in development and metabolism of human tissues and organs as well as a number of diseases, such as cancer, obesity, diabetes and osteoporosis. Co-regulators, one important kind of factors in the ER transcriptional signaling, increase(as co-activators) or reduce(as co-repressors)ER-mediated transcriptional activity via direct and indirect binding to ER. Increasing evidence has revealed that a short α-helical sequence LXXLL motif(where L is leucine, X is any amino acid), widely present in many co-regulators, especially co-activators, plays an essential or necessary role in co-regulator interaction with ER. To explore the involved mechanism(s) will be helpful in understanding the critical role of LXXLL motif in the interaction of co-regulators and ER. This review briefly describes the potential roles of LXXLL motif in the involvement of ER co-regulators in modulation of ER signaling and underlying mechanisms as well as current progress in developing pharmaceutical agents that modulate ER-coregulator interaction via specifically targeting LXXLL motifs in therapy of hormone-associated cancers.