A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice

Cell Reports
Liam C HuntFabio Demontis

Abstract

Skeletal muscle cell (myofiber) atrophy is a detrimental component of aging and cancer that primarily results from muscle protein degradation via the proteasome and ubiquitin ligases. Transcriptional upregulation of some ubiquitin ligases contributes to myofiber atrophy, but little is known about the role that most other ubiquitin ligases play in this process. To address this question, we have used RNAi screening in Drosophila to identify the function of > 320 evolutionarily conserved ubiquitin ligases in myofiber size regulation in vivo. We find that whereas RNAi for some ubiquitin ligases induces myofiber atrophy, loss of others (including the N-end rule ubiquitin ligase UBR4) promotes hypertrophy. In Drosophila and mouse myofibers, loss of UBR4 induces hypertrophy via decreased ubiquitination and degradation of a core set of target proteins, including the HAT1/RBBP4/RBBP7 histone-binding complex. Together, this study defines the repertoire of ubiquitin ligases that regulate myofiber size and the role of UBR4 in myofiber hypertrophy.

Citations

Feb 28, 2020·Journal of Applied Physiology·C Brooks MobleyJohn J McCarthy
Jul 9, 2020·International Journal of Molecular Sciences·Anna Vainshtein, Marco Sandri
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey J KeluSimon M Hughes
Jan 14, 2021·Nature Communications·Roberta SartoriMarco Sandri
Oct 15, 2020·American Journal of Physiology. Cell Physiology·David C HughesAdam P Sharples
Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dulce Peris-MorenoDaniel Taillandier
Feb 27, 2021·Biochemical Society Transactions·Heather A Baker, Jonathan P Bernardini
Mar 31, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Jawed A SiddiquiMohd W Nasser
May 27, 2021·American Journal of Physiology. Cell Physiology·Yusuke NishimuraYu-Chiang Lai

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE126922

Methods Mentioned

BETA
ubiquitination
transgenic
affinity purification
pulldown
immunoprecipitation
transfection
co-immunoprecipitation
PCR
electrophoresis
protein assay

Software Mentioned

- View
STRONGARM
MP
Lab
JUMP
Sequest
Proteome Discoverer
limma
Nikon Elements
DIOPT

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.