# Dissecting the developmental roles of the deubiquitinase Usp9x

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $45,520

## Abstract

Project Summary/Abstract
Mouse Embryonic Stem (ES) cells are derived from the Inner Cell Mass (ICM) just prior to implantation into the
uterus. In the embryo, they are pluripotent, i.e. they give rise to all cell types of the adult organism. When
maintained in specific culture conditions, ES cells propagate essentially indefinitely as pluripotent cells in vitro,
a property called self-renewal. As a result, ES cells are a useful system for understanding the mechanisms that
promote pluripotency versus lineage commitment in the embryo and have become essential to studies of
embryonic development and regeneration. Many studies have examined the transcriptional, epigenetic, and
signaling programs that contribute to ES cell self-renewal. Growing evidence suggests that the ubiquitin-
proteasome system (UPS) also reinforces ES cell identity. The UPS consists of a network of ubiquitin ligases,
enzymes that add ubiquitin to substrates; deubiquitinases (DUBs), which oppose the actions of ubiquitin
ligases; and the proteasome, which degrades ubiquitinated proteins. The contributions of DUBs to pluripotency
are still poorly understood, despite several examples of DUBs promoting self-renewal. In preliminary studies,
we have found that the DUB Usp9x promotes the open chromatin state and self-renewal capacity of ES cells.
We propose to study this protein in mouse ES cells and will test the hypothesis that Usp9x is an important
regulator of ES cell identity, promoting self-renewal by deubiquitinating and stabilizing key components of self-
renewal pathways. Specifically, we aim to dissect the role(s) of Usp9x in mouse ES cells by (1) analyzing the
consequences of Usp9x genetic deletion and mutation on ES cell self renewal and lineage induction (2) and by
identifying key substrates and interacting partners. This work aims to shed light on the interplay between the
ubiquitin-proteasome system and self-renewal programs. It is highly relevant to studies of molecular
mechanisms underlying intellectual and developmental disability and has the potential to offer insight into how
USP9X deregulation promotes human developmental disorders, neurological syndromes, and cancer.

## Key facts

- **NIH application ID:** 9969455
- **Project number:** 5F30HD093116-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Trisha A. Macrae
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969455

## Citation

> US National Institutes of Health, RePORTER application 9969455, Dissecting the developmental roles of the deubiquitinase Usp9x (5F30HD093116-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9969455. Licensed CC0.

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