Open Access<p>MDM2-C Functions as an E3 Ubiquitin Ligase</p>
Author(s) -
Jun Yeob Kim,
Rusia Lee,
Gu Xiao,
Dominique Forbes,
Jill Bargonetti
Publication year - 2020
Publication title -
cancer management and research
Language(s) - Portuguese
Resource type - Journals
SCImago Journal Rank - 1.024
H-Index - 40
ISSN - 1179-1322
DOI - 10.2147/cmar.s260943
Subject(s) - mdm2 , ubiquitin ligase , ubiquitin , context (archaeology) , dna ligase , biology , mutant , gene isoform , microbiology and biotechnology , cancer research , biochemistry , genetics , cell culture , gene , paleontology
Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase that is over-expressed in many cancers and regulates target proteins through ubiquitination. Full-length MDM2 (MDM2-FL) is best known for targeting wild-type p53 for degradation by the proteasome, but the functions of the many splice variants of MDM2 are under-explored. The three well-studied alternative MDM2 isoforms are MDM2-A/ALT2, MDM2-B/ALT1, and MDM2-C/ALT3. MDM2-A and MDM2-B are capable of down-regulating MDM2-FL activity and have transforming activity in cancers with mutant p53. The MDM2 isoform MDM2-C is over-expressed in breast cancer and correlates with decreased survival in the context of mutant p53 expression. Therefore, MDM2-C requires further study to determine if it has biochemical activities similar to MDM2-FL. Hypothesis: We hypothesized that like MDM2-FL, the MDM2-C isoform (lacking exons 5-9 and containing a full C-terminal RING finger sequence) would maintain E3 ubiquitin ligase activity.