Abstract 3702: Src phosphorylated Mdm2 requires MdmX to act as a neddylating ligase

Abstract

Abstract Mdm2 is an oncoprotein and, along with its family member MdmX, have been shown to be elevated in human cancers. Like Mdm2, MdmX, is a RING containing protein, yet it lacks intrinsic E3 ligase function. Mdm2 has been shown to facilitate ubiquitination as a monomer, a homodimer, and as a heterodimer with MdmX depending on the cellular stress. Our recent report establishes that under growth conditions that activate Src, Mdm2 functions as a neddylating enzyme. Whether MdmX is necessary for Mdm2 to neddylate p53 has yet to be shown. Here we demonstrate that Src phosphorylation results in increased levels of MdmX, increased binding between Mdm2 and MdmX, and increased neddylation of MdmX and p53. Interestingly, the lack of MdmX (in transient assays or in shRNA cell lines) results in decreased neddylation of p53. These data support a critical role for MdmX as part of the Mdm2 neddylating complex. Citation Format: Paula M. Hauck, Lindsey D. Mayo. Src phosphorylated Mdm2 requires MdmX to act as a neddylating ligase. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3702.