Tau protein binds to the P53 E3 ubiquitin ligase MDM2.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 06 2023
23 06 2023
Historique:
received:
09
01
2023
accepted:
14
06
2023
medline:
26
6
2023
pubmed:
24
6
2023
entrez:
23
6
2023
Statut:
epublish
Résumé
Tau gene mutations cause a progressive dementia and neurotoxic Tau forms deposited in neurofibrillary tangles are hallmarks of neurodegenerative tauopathies. Loss of non-canonical Tau functions may contribute to disease. In fact, Tau depletion affects the cellular response to DNA damage and tauopathies exhibit the accumulation of DNA lesions. Moreover, Tau modulates P53 activity and cell fate. Considering that MDM2 is the main antagonist of P53, we investigated, using orthogonal assays, if Tau interacts with MDM2. We report the existence in cells and brain of a Tau-MDM2 complex that, in vitro, exhibits reduced P53 ubiquitination activity in a manner sensitive to a Tau mutation. The Tau-MDM2 interaction involves the microtubule-binding domain of Tau and the acidic domain of MDM2, reminiscent of the binding of Tau to negatively charged microtubules. Notably, MDM2 accumulates aberrantly in neurofibrillary tangles. Aging-associated insults may expose a novel loss-of-function of Tau in neurodegeneration and cancer.
Identifiants
pubmed: 37353565
doi: 10.1038/s41598-023-37046-8
pii: 10.1038/s41598-023-37046-8
pmc: PMC10290082
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Tumor Suppressor Protein p53
0
tau Proteins
0
MDM2 protein, human
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10208Informations de copyright
© 2023. The Author(s).
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