Organ defects of the Usp7^K444R mutant mouse strain indicate the essential role of K63-polyubiquitinated Usp7 in organ formation.

ABSTRACT:

Background

K63-linked polyubiquitination of proteins have nonproteolytic functions and regulate the activity of many signal transduction pathways. USP7, a HIF1α deubiquitinase, undergoes K63-linked polyubiquitination under hypoxia. K63-polyubiquitinated USP7 serves as a scaffold to anchor HIF1α, CREBBP, the mediator complex, and the super elongation complex to enhance HIF1α-induced gene transcription. However, the physiological role of K63-polyubiquitinated USP7 remains unknown.

Methods

Using a Usp7^K444R point mutation knock-in mouse strain, we performed immunohistochemistry and standard molecular biological methods to examine the organ defects of liver and kidney in this knock-in mouse strain. Mechanistic studies were performed by using deubiquitination, immunopr

SUBMITTER: Wu HT 

PROVIDER: S-EPMC10104958 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature