The role of SUMO modifications on estrogen receptor function by kinase signaling pathways

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Recently, the identification of SUMOylation, the process by which SUMO, a small ubiquitin-like modifier, is covalently linked to target proteins, has emerged as a new protein modification that regulates the function of an increasing number of transcription factors. The functional consequences of SUMOylation are not understood at the molecular level, but with recent observations that nuclear receptors were reported to be SUMOylated, this raises the interesting possibility that SUMOylation may serve as a novel mechanism by which hormonal signaling pathways may regulate transcription.Our expertise in the study of nuclear receptors has mainly arise from our work on estrogen receptors ERa and ERb. With the identification of ERb, our reevaluation of ER activation pathways has allowed to recognize that ERa and ERb are selectively regulated by growth factors of the EGF family which direct ER phosphorylation, therefore providing a potential of ERs to undergo posttranslational modifications. These studies therefore uncover novel aspects on how non hormonal mediated pathways may regulate transcription by estrogen receptors.With the emerging evidence that SUMOylation represents a novel mechanism in ER functions that has not received widespread attention, and based on the rising concept that phosphorylation and SUMOylation are intimately associated to regulate transcription factors, these studies aim at defining a functional coupling between these two multisite posttranslational modifications of estrogen receptors to integrate their transcriptional competence and cellular functions.