# The role of Fbxl22 in the regulation of skeletal muscle mass

> **NIH NIH K01** · UNIVERSITY OF IOWA · 2021 · $120,420

## Abstract

Project Summary/Abstract
Skeletal muscle atrophy occurs as a consequence of many chronic diseases and conditions such as
disuse. Central to the process of muscle atrophy is protein degradation, for which the E3 ubiquitin
ligases are critical in targeting specific proteins for degradation. The roles of many E3 ubiquitin
ligases in muscle are unknown and specific substrates have yet to be identified. The overall objective
of this proposal is to determine the role of the E3 ligase, F-box and leucine-rich repeat protein 22
(Fbxl22), in skeletal muscle atrophy. My central hypothesis is that Fbxl22 is necessary for the
process of muscle atrophy. Robust preliminary data supports this hypothesis: 1) Fbxl22 mRNA
expression is induced after 3 days in a model of neurogenic muscle atrophy, 2) Overexpression of
Fbxl22 in hindlimb muscles results in significant elevations of total ubiquitinated proteins. I propose
two specific aims:
 Specific Aim 1: Determine the functional role of Fbxl22 isoforms in skeletal muscle atrophy,
injury and regrowth. I will address this aim using knockdown and overexpression of Fbxl22 gene
isoforms in a model of neurogenic muscle atrophy and assess Fbxl22 isoform expression in an acute
muscle injury model.
 Specific Aim 2: To identify substrate targets for Fbxl22-dependent ubiquitination. I will
address this aim using a combined approach of Fbxl22 gene manipulation with proteomics analysis
and post-translational modification identification of ubiquitin motifs on Fbxl22-dependent substrates.
 With the completion of this proposal, I expect to have identified novel mechanisms for
understanding the muscle atrophy process. By identifying the mechanisms of skeletal muscle
atrophy, we can explore new therapeutic strategies for improving an individual’s quality of life where
muscle wasting is present.
 The University of Iowa has a longstanding history of support to its trainees and junior faculty.
My mentor, Prof. Bodine is a world leader in skeletal muscle physiology, atrophy and hypertrophy.
This K01 award will expand my research skills in ubiquitin proteomics and skeletal muscle atrophy.
These tools may enable the identification of new therapeutic strategies for alleviating the detrimental
impact of skeletal muscle wasting.

## Key facts

- **NIH application ID:** 10213467
- **Project number:** 1K01AR077684-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** David C Hughes
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $120,420
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213467

## Citation

> US National Institutes of Health, RePORTER application 10213467, The role of Fbxl22 in the regulation of skeletal muscle mass (1K01AR077684-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213467. Licensed CC0.

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