Small molecule MMRi62 targets MDM4 for degradation and induces leukemic cell apoptosis regardless of p53 status

Small molecule MMRi62 targets MDM4 for degradation and induces leukemic cell apoptosis regardless of p53 status

MDM2 and MDM4 proteins are key negative regulators of tumor suppressor p53. MDM2 and MDM4 interact via their RING domains and form a heterodimer polyubiquitin E3 ligase essential for p53 degradation. MDM4 also forms heterodimer E3 ligases with MDM2 isoforms that lack p53-binding domains, which regul...

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Bibliographic Details
Main Authors: Rati Lama, Chao Xu, Samuel L. Galster, Javier Querol-García, Scott Portwood, Cory K. Mavis, Federico M. Ruiz, Diana Martin, Jin Wu, Marianna C. Giorgi, Jill Bargonetti, Eunice S. Wang, Francisco J. Hernandez-Ilizaliturri, Gerald B. Koudelka, Sherry R. Chemler, Inés G. Muñoz, Xinjiang Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Oncology
Subjects:
MDM2
MDM4
E3 ligase
degradation
apoptosis
leukemia
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.933446/full

Internet

https://www.frontiersin.org/articles/10.3389/fonc.2022.933446/full

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