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Hdm2 disrupts HdmX-mediated nuclear export of p53 by sequestering it in nucleus.
- Source :
-
Experimental cell research [Exp Cell Res] 2024 Aug 15; Vol. 441 (2), pp. 114185. Date of Electronic Publication: 2024 Jul 26. - Publication Year :
- 2024
-
Abstract
- Dysfunction of the tumor suppressor p53 occurs in most human cancers, Hdm2 and HdmX play critical roles in p53 inactivation and degradation. Under unstressed conditions, HdmX binds to p53 like Hdm2, but HdmX cannot directly induce p53 degradation. Moreover, HdmX has been reported to stimulate Hdm2-mediated ubiquitination and degradation of p53. Here we reported that HdmX promoted the nuclear export of p53 independent of Hdm2 in living cells using FRET technology. Whereas, Hdm2 impeded HdmX-mediated nuclear export of p53 by sequestering it in nucleus. Interestingly, the C-terminal RING domain mutant Hdm2 <superscript>C464A</superscript> formed heterooligomers with p53 in nucleus, which was inhibited by HdmX. The heterooligomers were located near PML-NBs. This study indicate that the nuclear Hdm2-HdmX interaction aborts the HdmX-mediated nuclear export of p53.<br />Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Nuclear Proteins metabolism
Nuclear Proteins genetics
Ubiquitination
Protein Binding
Tumor Suppressor Protein p53 metabolism
Tumor Suppressor Protein p53 genetics
Proto-Oncogene Proteins c-mdm2 metabolism
Active Transport, Cell Nucleus
Cell Nucleus metabolism
Proto-Oncogene Proteins metabolism
Cell Cycle Proteins metabolism
Cell Cycle Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 441
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 39069150
- Full Text :
- https://doi.org/10.1016/j.yexcr.2024.114185