This entry represents the MDM2-binding protein (MTBP). MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53, leading to its degradation by the proteasome []. MTBP inhibits autoubiquitination of MDM2, thereby enhancing MDM2 stability, and this promotes MDM2-mediated ubiquitination of p53 and its subsequent degradation []. Mouse MTBP also inhibits cancer cell migration by interacting with alpha-actinin-4 (ACTN4) [].
This entry represents the central domain of the MDM2-binding protein (MTBP). MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53, leading to its degradation by the proteasome []. MTBP inhibits autoubiquitination of MDM2, thereby enhancing MDM2 stability, and this promotes MDM2-mediated ubiquitination of p53 and its subsequent degradation []. Mouse MTBP also inhibits cancer cell migration by interacting with alpha-actinin-4 (ACTN4) [].
This entry represents the N-terminal domain of the MDM2-binding protein (MTBP). MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53, leading to its degradation by the proteasome []. MTBP inhibits autoubiquitination of MDM2, thereby enhancing MDM2 stability, and this promotes MDM2-mediated ubiquitination of p53 and its subsequent degradation []. Mouse MTBP also inhibits cancer cell migration by interacting with alpha-actinin-4 (ACTN4) [].
This entry represents the C-terminal domain of the MDM2-binding protein (MTBP). MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53, leading to its degradation by the proteasome []. MTBP inhibits autoubiquitination of MDM2, thereby enhancing MDM2 stability, and this promotes MDM2-mediated ubiquitination of p53 and its subsequent degradation []. Mouse MTBP also inhibits cancer cell migration by interacting with alpha-actinin-4 (ACTN4) [].
MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome []. p53 acts as an important defense mechanism against cancer, and is negatively regulated by interaction with the oncoprotein MDM2 []. MDM2 overexpression correlates with metastasis and advanced forms of several cancers and may be used as a cancer drug target []. In addition, MDM2 has important roles in the cell independent of p53. It interacts with several proteins such as Rb/E2F-1 complex [], the DNA methyltransferase DNMT3A [], p107 [], MTBP []and the cyclin kinase inhibitor p21 []. MDM2 also affects cell apoptosis [, ]. The core of MDM2 folds into an open bundle of four helices which is capped by two small 3-strandedβ-sheets. It consists of a duplication of two structural repeats. MDM2 has a deep hydrophobic cleft on which the p53 α-helix binds; p53 residues involved in transactivation are buried deep within the cleft of MDM2, thereby concealing the p53 transactivation domain. In addition to its N-terminal p53 binding domain, MDM2 contains a central acidic domain, zinc finger domain and a C-terminal RING-finger domain.
MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome []. p53 acts as an important defense mechanism against cancer, and is negatively regulated by interaction with the oncoprotein MDM2 []. MDM2 overexpression correlates with metastasis and advanced forms of several cancers and may be used as a cancer drug target []. In addition, MDM2 has important roles in the cell independent of p53. It interacts with several proteins such as Rb/E2F-1 complex [], the DNA methyltransferase DNMT3A [], p107 [], MTBP []and the cyclin kinase inhibitor p21 []. MDM2 also affects cell apoptosis [, ].MDM2 contains an N-terminal p53-binding domain, and a C-terminal modified C2H2C4-type RING-HC finger conferring E3 ligase activity that is required for ubiquitination and nuclear export of p53. It is also responsible for the hetero-oligomerization of MDM2, which is crucial for the suppression of P53 activity during embryonic development, and the recruitment of E2 ubiquitin-conjugating enzymes []. MDM2 also harbours a RanBP2-type zinc finger (Znf-RanBP2) domain, as well as a nuclear localisation signal (NLS) and a nuclear export signal (NES), near the central acidic region. The Znf-RanBP2 domain plays an important role in mediating MDM2 binding to ribosomal proteins and thus is involved in MDM2-mediated p53 suppression.This entry represents the C-terminal modified C2H2C4-type RING-HC finger.
