What is it about?

SET plays oncogenic roles in many cancers, where it functions as an inhibitor of tumor suppressor PP2A. However, molecular details of specific interactions between SET and PP2A as well as the interactions between SET and sphingolipid analogue drug FTY720 or ceramide have been largely unknown. Here, we provide NMR-guided molecular details of SET-FTY720 and SET-ceramide interactions. The data presented in this study provides a possible mechanism by which ceramide or FTY720 interacts with SET, leading to the activation of specific PP2A holoenzyme. These data might have important implications to target SET for PP2A activation, as ceramide/PP2A signaling axis is known to play key roles in the regulation of tumor suppression, insulin resistance, and vascular dysfunction in metabolic disease.

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Why is it important?

This work proposes a possible alternative mechanism for the activation of PP2A by targeting SET. It also provides more detail about the interaction between SET and FTY720 or ceramide. Since SET plays a role in many cancers these molecular details may help drive drug discovery/design of SET-targeting compounds.

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This page is a summary of: The NMR-based characterization of the FTY720-SET complex reveals an alternative mechanism for the attenuation of the inhibitory SET-PP2A interaction, The FASEB Journal, March 2019, Federation of American Societies For Experimental Biology (FASEB), DOI: 10.1096/fj.201802264r.
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