# Novel Insights into the Molecular Mechanisms Governing Mdm2 Ubiquitination and Destruction

 Title: Novel Insights into the Molecular Mechanisms Governing Mdm2 Ubiquitination and Destruction Author: Fukushima, Hidefumi; Inuzuka, Hiroyuki; Shaik, Shavali; Wei, Wenyi Note: Order does not necessarily reflect citation order of authors. Citation: Inuzuka, Hiroyuki, Hidefumi Fukushima, Shavali Shaik, and Wenyi Wei. 2010. Novel insights into the molecular mechanisms governing Mdm2 ubiquitination and destruction. Oncotarget 1(7): 685-690. Full Text & Related Files: 3248122.pdf (1.320Mb; PDF) Abstract: The Mdm2/p53 pathway is compromised in more than 50% of all human cancers, therefore it is an intensive area of research to understand the upstream regulatory pathways governing Mdm2/p53 activity. Mdm2 is frequently overexpressed in human cancers while the molecular mechanisms underlying the timely destruction of Mdm2 remain unclear. We recently reported that Casein Kinase I phosphorylates Mdm2 at multiple sites to trigger Mdm2 interaction with, and subsequent ubiquitination and destruction by the SCF$$^{\beta-TRCP}$$ E3 ubiquitin ligase. We also demonstrated that the E3 ligase activity-deficient Mdm2 was still unstable in the G1 phase and could be efficiently degraded by SCF$$^{\beta-TRCP}$$. Thus our finding expands the current knowledge on how Mdm2 is tightly regulated by both self- and SCF$$^{\beta-TRCP}$$-dependent ubiquitination to control p53 activity in response to stress. It further indicates that loss of β-TRCP or Casein Kinase I function contributes to elevated Mdm2 expression that is frequently found in various types of tumors. Published Version: www.impactjournals.com/oncotarget Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248122/pdf/ Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:9369051