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Stress-Induced Alternative Splice Forms Of Mdm2 And Mdmx Modulate The P53-Pathway In Distinct Ways, Matthew F. Rouhier, Aishwarya G. Jacob, Ravi K. Singh, Daniel F. Comiskey Jr, Fuad Mohammad, Thomas W. Bebee, Dawn S. Chandler
Stress-Induced Alternative Splice Forms Of Mdm2 And Mdmx Modulate The P53-Pathway In Distinct Ways, Matthew F. Rouhier, Aishwarya G. Jacob, Ravi K. Singh, Daniel F. Comiskey Jr, Fuad Mohammad, Thomas W. Bebee, Dawn S. Chandler
Matthew F Rouhier
MDM2 and MDMX are the chief negative regulators of the tumor-suppressor protein p53 and are essential for maintaining homeostasis within the cell. In response to genotoxic stress and also in several cancer types, MDM2 and MDMX are alternatively spliced. The splice variants MDM2-ALT1 and MDMX-ALT2 lack the p53-binding domain and are incapable of negatively regulating p53. However, they retain the RING domain that facilitates dimerization of the full-length MDM proteins. Concordantly, MDM2-ALT1 has been shown to lead to the stabilization of p53 through its interaction with and inactivation of full-length MDM2. The impact of MDM2-ALT1 expression on the p53 pathway …