Abstract
Mdm2 is a crucial negative regulator of the tumor suppressor function of p53. However, little is known about Mdm2 protein stability regulation by other tumor suppressors. Nuclear receptor small heterodimer partner (SHP, NROB2) functions as a tumor suppressor in liver cancer. We show here a surprising finding of a feedback regulatory loop between SHP and Mdm2. SHP stabilizes Mdm2 protein by abrogating Mdm2 self-ubiquitination, and Mdm2 in turn attenuates SHP protein levels under p53-deficient conditions. Such cross-regulation critically depends on the physical interaction of SHP with Mdm2 through the SHP K170 residue. The Mdm2–SHP interplay represents a novel component of Mdm2 signaling that is likely to dictate Mdm2 activity and function. Structured summary of protein interactions:MDM2physically interacts with SHP by anti tag coimmunoprecipitation (View Interaction: 1, 2)SHPphysically interacts with MDM2 by anti bait coimmunoprecipitation (View Interaction: 1, 2)MDM2physically interacts with p53 by anti tag coimmunoprecipitation (View Interaction: 1, 2)SHPphysically interacts with p53 by anti bait coimmunoprecipitation (View Interaction: 1, 2)p53physically interacts with SHP by anti tag coimmunoprecipitation (View interaction)
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