Cocompartmentalization of p53 and Mdm2 is a major determinant for Mdm2-mediated degradation of p53

Experimental Cell Research

Volumn 270, Issue 1, 2001, Pages 66-77

  Xirodimas, Dimitris P ^a   Stephen, Charles W ^a   Lane, David P ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

Cocompartmentalization; Cytoplasmic degradation; Leptomycin B; Mdm2; Nuclear export; P53; Ubiquitination

Indexed keywords

MUTANT PROTEIN; PROTEASOME; PROTEIN MDM2; PROTEIN P53;

ARTICLE; BIOACCUMULATION; CELL COMPARTMENTALIZATION; CELL LEVEL; CELL NUCLEUS; CONTROLLED STUDY; CYTOPLASM; ENZYME INHIBITION; GENE MUTATION; HUMAN; HUMAN CELL; MOLECULAR MODEL; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; STEADY STATE;

HUMAN IMMUNODEFICIENCY VIRUS; NES;

EID: 0035887286     PISSN: 00144827     EISSN: None     Source Type: Journal    
DOI: 10.1006/excr.2001.5314     Document Type: Article

References (46)

1. p53, the cellular gatekeeper for growth and division
2. Regulation of the p53 tumor suppressor protein
3. p53 - Puzzle and paradigm
4. MDM2-arbiter of p53's destruction
5. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53
6. Rescue of early embryonic lethality in Mdm2-deficient mice by deletion of p53
7. Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo
8. Regulation of p53 stability by Mdm2
9. Mdm2 promotes the rapid degradation of p53
10. Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein
11. Accumulating active p53 in the nucleus by inhibition of nuclear export: A novel strategy to promote the p53 tumor suppressor function
12. An inhibitor of nuclear export activates the p53 response and induces localisation of HDM2 and p53 to U1A-positive nuclear bodies associated with the PODs
13. A leucine-rich nuclear export signal in the p53 tetramerization domain: Regulation of subcellular localization and p53 activity by NES masking
14. Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53
15. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
16. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase
17. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53
18. ARF peptide blocks Mdm2-dependent ubiquitination in vitro and can activate p53 in vivo
19. The Ink4a tumor suppressor gene product, p19(Arf), interacts with MDM2 and neutralizes MDM2's inhibition of p53
20. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways
21. Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
22. Different effects of p14ARF on the levels of ubiquitinated p53 and Mdm2 in vivo
23. Nucleolar Arf sequesters Mdm2 and activates p53
24. Mutations in human ARF exon 2 disrupt its nucleolar localization and impair its ability to block nuclear export of MDM2 and p53
25. P19 (ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2
26. Analysis of p53 expression in human tumours: An antibody raised against human p53 expressed in Escherichia coli
27. Characterisation of epitopes on human p53 using phage-displayed peptide libraries: Insights into antibody-peptide interactions
28. Mapping of the p53 and mdm-2 interaction domains
29. The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2
30. SUMO-1 modification activates the transcriptional response of p53
31. Molecular evolution of the thermosensitive PAb1620 epitope of human p53 by DNA shuffling
32. p53 protein stability in tumor cells is not determined by mutation but is dependent on Mdm2 binding
33. Multiple C-terminal lysine residues target p53 for ubiquitin-proteasome-mediated degradation
34. Multiple lysine mutations in the C-terminal domain of p53 interfere with MDM2-dependent protein degradation and ubiquitination
35. Nuclear accumulation of P53 protein is mediated by several nuclear-localization signals and plays a role in tumorigenesis
36. An intact HDM2 RING-finger domain is required for nuclear exclusion of p53
37. The MDM2 RING-finger domain is required to promote p53 nuclear export
38. Cytoplasmically "sequestered" wild type p53 protein is resistant to Mdm2-mediated degradation
39. Identification of a cryptic nucleolar-localization signal in MDM2
40. p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2
41. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain
42. p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage
43. Nine hydrophobic side chains are key determinants of the thermodynamic stability and oligomerization status of tumor suppressor p53 tetramerization domain
44. DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization
45. Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2
46. MDM2-dependent ubiquitination of nuclear and cytoplasmic P53